Thrombocytopenia Causes and Treatments

Conquer Low Platelets

Alternative And Natural Therapies For Itp (idiopathic Thrombocytopenia Purpura). Live Free From Itp. Complete Program To Increase Platelets. This Is What You Will Learn With this Guide: The Two Herbs That can help bring up your platelets. The Two Vitamins needed to keep those platelets from dropping. What foods may cause your platelets to drop. How science has confirmed the benefits of these herbs in their use with low platelets. Why your doctor may not know about these natural alternatives and how you can assist him in helping you. Different tests that naturopathic doctors do to determine your real state of health that may reverse the course of your body drastically. Understand some of the reasons why people develop low platelets. Discover how your digestive tract may be the culprit to your low platelet level problems. How you can prevent the most drastic step a splenectomy. How you can restore your health so that you dont need any more dangerous drugs. Get your life back and stop ending up in the hospital all the time. Learn why your immune system is attacking your platelets and how to calm it down. Learn what over the counter medications to stay away from if you have low platelets Read more here...

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Human Immunodeficiency Virus Thrombocytopenia

Thrombocytopenia is a relatively frequent complication of HIV-1 infection. Thrombocytopenia is seen in 3-8 of seropositive individuals and 30-45 of patients with fully developed acquired immunodeficiency syndrome (AIDS). During the initial phases of HIV infection, thrombocytopenia may be the only manifestation of HIV infection and is immunologically mediated (HIV-ITP). However, patients with late-stage HIV-1 infection (AIDS) have anemia, leukopenia, and thrombocy-topenia due to direct marrow suppression by the virus. Other factors contributing to thrombocytopenia are other infections (e.g., Pneumocystis carinii pneumonia, Mycobacterium avium, cytomegalovirus CMV ), myelosuppressive drugs, chronic DIC, and severe malnutrition. In addition to steroids, anti-D, and IVIG, dapsone, vincristine, zidovudine, didano-sine, and splenectomy have been used to treat HIV-related thrombocytopenia.

Heparin Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is defined by a fall in the platelet count to less than 150,000 mm3, or a decrease in the platelet count by 50 in patients with preexisting thrombocytopenia. It is due to an autoantibody directed against heparin in association with platelet factor 4. This antibody binds to and activates the Fc receptor on the platelet surface leading to platelet activation. HIT occurs 5 or more days after starting heparin, if the patient has not received heparin before. In patients with previous exposure, it can develop within 48 hours. In patients with suspected HIT, heparin should be discontinued immediately. Alternative anticoagulation therapy (discussed on pages 354-355) should be utilized. If the patient has arterial or venous thrombosis, low-molecular-weight heparin (LMWH) or warfarin should not be used. There is a high risk of cross-reactivity between LMWH and heparin-dependent antibody. Warfarin can lead to skin necrosis or worsening of thrombosis.

Drug Induced Thrombocytopenia

Drugs can cause thrombocytopenia by two different mechanisms marrow depression and increased platelet destruction. A marrow examination will distinguish between thrombocytopenia caused by toxic depression, in which the megakaryocytes are scanty or absent, and thrombocytopenia resulting from peripheral destruction, in which the megakaryocytes are normal or increased in number. These patients usually present with sudden onset of bleeding 1-2 weeks after starting the drug and have severe thrombocytopenia. The platelet count begins to rise within a few days after discontinuing the drug. A high index of clinical suspicion is required to make the diagnosis. The sensitivity of in vitro assays is relatively low. Treatment is IVIG or steroids. Table 10-4 lists the drugs proved or suspected to induce drug-dependent antibody-mediated immune thrombocytopenia.

Neonatal Thrombocytopenia

Neonates with severe thrombocytopenia may have bleeding that leads to lifelong residual defects (e.g., intracranial hemorrhage) or death. The incidence of neonatal thrombocytopenia (cord blood platelet count < 50,000 mm3) is 0.3 and that of severe neonatal thrombocytopenia (platelet count < 20,000 mm3) is 0.04 . Most infants who have thrombocytopenia appear ill, are premature, and have other disorders that contribute to the thrombocytopenia, including bacteremia and DIC. In these sick infants, the incidence of thrombocytopenia is as high as 15 and it is most severe several days after delivery. Table 10-8 lists the causes of neonatal thrombocytopenia, and Figure 10-3 shows an approach to the diagnosis of thrombocytopenia in the infant. Table 10-8. Causes of Neonatal Thrombocytopenia thrombocytopenia) b. Maternal drug-induced thrombocytopenia E. Inherited thrombocytopenia II. Decreased or absent megakaryocytes in the marrow (amegakaryocytic thrombocytopenia) 1. Thrombocytopenia...

Cytokines In The Treatment Of Thrombocytopenia

Cytokines that stimulate platelet production may act on early, uncommitted progenitors promoting commitment along the megakaryocytic (MK) lineage or may promote survival so that this commitment can occur without a direct influence. Cytokines with potential activity on platelet production currently available for clinical testing include the following interleukin-3 (IL-3), stem cell factor (SCF), IL-6, IL-11, and thrombopoietin (TPO). IL-11 and TPO have been used in clinical trials to ameliorate chemotherapy-induced thrombocytopenia. However, they have significant side effects and are not routinely used. Trials regarding use of cytokines in treatment of thrombocytopenia are ongoing.

Inherited Thrombocytopenia

Sex-Linked Thrombocytopenias Thrombocytopenia with a sex-linked pattern of inheritance has been reported in a number of families. The presence of a normal number of megakaryocytes in the bone marrow suggests that the thrombocytopenia is a result of shortened platelet survival due to an intrinsic platelet defect. The response to steroids is poor. A complete response to splenectomy has occurred in some patients. X-linked anemia with severe thrombocytopenia, due to defects in the GATA-1 gene, has been reported. Bone marrow shows many large megakaryocytes with nuclei pushed to the side and unorganized granular content. The Wiskott-Aldrich is an X-linked syndrome consisting of eczema, recurrent infections, and thrombocytopenia. The gene involved is on the short arm of the X chromosome. It has been cloned and designated WASp. Infants are ill from the first few months of life and die in early childhood. Bleeding is frequently ushered in by melena during the neonatal period, later followed by...

Normal or Increased Megakaryocytes in the Marrow Megakaryocyte Thrombocytopenia

Pregnant women with ITP are at a 50 risk for delivering thrombocytopenic infants, whether or not the mother is thrombocytopenic during pregnancy or at the time of delivery. This results from the transplacental passage of maternal IgG autoantibod-ies into the fetal circulation, with destruction of fetal platelets. Although self-limiting, neonatal ITP (NITP) may last for several weeks. Infants with severe thrombocytopenia (platelet counts < 50,000 mm3) have a 1 risk for intracranial hemorrhage (ICH). The risk of severe neonatal thrombocytopenia appears higher if the mother has had a previously affected fetus. True maternal ITP must be distinguished from gestational thrombocytopenia. This is a common disorder, in which maternal thrombocytopenia is not severe (platelet counts > 100,000 mm3) and infants are not at risk for thrombocytopenia. Mother with thrombocytopenia (< 100,000 mm3) in the current pregnancy. Treatment a. IVGG therapy, 1 g kg day administered weekly, is recommended...

Immune Dysregulation Polyendocrinopathy Enteropathy XLinked Inheritance Model for Autoaggression

Patients with the rare X-linked syndrome, immune dysregulation, polyendocrinopathy, enteropathy (IPEX) may present early in life with type I diabetes, hyperthyroidism, chronic enteropathy, villous atrophy, dermatitis, autoimmune hemolytic anemia, and antibody- induced neutropenia and thrombocytopenia. Of the reported families with IPEX, most affected boys died before the age of 3 years of malabsorbtion, failure to thrive, infections, or other complications. Characteristic findings at autopsy include lymphocytic infiltrates affecting the lungs, endocrine organs, such as pancreas and thyroid and skin, and increased lymphoid elements in lymph nodes and spleen. Although symptomatic therapy with immunosuppressive drugs provides some beneficial effects, the only curative treatment is hematopoietic stem cell transplantation.

Diagnoses and Treatment of IPEX

The diagnoses of IPEX should be considered in any young male patient presenting with intractable diarrhea, villous atrophy, and failure to thrive. The presence of an erythematous rash, eczema, or psoriasiform dermatitis strongly supports this diagnosis. Early onset of type 1 diabetes in a male patient with gastrointestinal symptoms and eczema is highly suspicious of IPEX. Autoimmune hemolytic anemia, thrombocytopenia, or neutropenia are not always present or may occur at a later age. The diagnoses of IPEX is highly suspect by demonstrating the absence of CD4+ CD25+ FOXP3+ Treg cells and is confirmed by mutation analysis of the FOXP3 gene. If the mutation in a given family is known, carrier females can be identified and prenatal diagnosis performed in a male fetus by sequence analysis of FOXP3 using DNA extracted from chorionic villous biopsies or cultured amniocytes.

Noninfectious inflammatory conditions

Marked proliferative synovitis speaks against the diagnosis of SLE. Erosive disease is rare, but the presence of reversible deformity is not. Other clinical features, such as serositis, fever, skin rash, and renal disease, may provide clues to the diagnosis. Laboratory abnormalities can include the presence of serum antinuclear antibodies, anemia, and thrombocytopenia (see Cha.pter 30).

Monitoring and Managing Adverse Drug Reactions

The nurse monitors the patient for leukopenia and thrombocytopenia. Leukopenia may result in signs and symptoms of an infection, such as fever, sore throat, and cough. The nurse protects the patient with leukope-nia from individuals who have an infection. With severe leukopenia the patient may be placed in protective (reverse) isolation. Thrombocytopenia is manifested by easy bruising and unusual bleeding following moderate to slight trauma to the skin or mucous membranes. The extremities of the patient with thrombocytopenia are handled with care to prevent bruising. Care is taken to prevent trauma when the patient is moved. The nurse inspects the skin daily for the extent of bruising and evidence of exacerbation of existing ecchymotic areas. It is important to encourage the patient to use a soft-bristled toothbrush to prevent any trauma to the mucous membranes of the oral cavity. The nurse reports any signs of leukopenia or thrombocytopenia immediately because this is an indication...

Other Adverse Reactions

Other adverse reactions associated with penicillin are hematopoietic changes such as anemia, thrombocy-topenia (low platelet count), leukopenia (low white blood cell count), and bone marrow depression. When penicillin is given orally, glossitis (inflammation of the tongue), stomatitis (inflammation of the mouth), dry mouth, gastritis, nausea, vomiting, and abdominal pain occur. When penicillin is given intramuscularly (IM), there may be pain at the injection site. Irritation of the vein and phlebitis (inflammation of a vein) may occur with intravenous (IV) administration.

Contraindications Precautions And Interactions

When linezolid is used with antiplatelet drugs such as aspirin or the NSAIDs (see Chap. 18) there is an increased risk of bleeding and thrombocytopenia. When administered with the MAOIs (see Chap. 31) the effects of the MAOIs are decreased. There is a risk of severe hypertension if linezolid is combined with large amounts of food containing tyramine (eg, aged cheese, caffeinated beverages, yogurt, chocolate, red wine, beer, pepperoni).

Adverse Reactions

More than half of the patients receiving this drug by the parenteral route experience some adverse reaction. Severe and sometimes life-threatening reactions include leukopenia (low white blood cell count), hypoglycemia (low blood sugar), thrombocytopenia (low platelet count), and hypotension (low blood pressure). Moderate or less severe reactions include changes in some laboratory tests, such as the serum creatinine and liver function tests. Other adverse reactions include anxiety, headache, hypotension, chills, nausea, and anorexia. Aerosol administration may result in fatigue, a metallic taste in the mouth, shortness of breath, and anorexia.

Neutropenia Associated with Metabolic Diseases

The presenting clinical features in neutropenia associated with metabolic diseases (Table 9-6) are lethargy, vomiting, ketosis, and dehydration during the neonatal period, failure to thrive, and growth retardation. The marrow is hypoplastic in these conditions, with decreased numbers of myeloid precursors. Idiopathic hyperglycin-emia and methylmalonic acidemia also have associated thrombocytopenia.

Promoting an Optimal Response to Therapy

The antiviral drugs are not given intramuscularly or subcutaneously. It is important to prepare the antiviral drugs according to the manufacturer's directions. The administration rate is ordered by the primary health care provider. The nurse takes care to prevent trauma because even slight trauma can result in bruising if the platelet count is low. If injections are given, pressure is applied at the injection site to prevent bleeding. Occasionally, headache or a slight fever may occur in patients taking antiviral drugs. An analgesic may be prescribed to manage these effects.

Cyanotic Congenital Heart Disease

Thrombocytopenia frequently occurs in children with severe cyanotic congenital heart disease, usually when the hematocrit levels are more than 65 and when the arterial oxygen saturation is less than 65 . This may be due to margination of platelets in the small blood vessels, which may occur in the presence of a high he-matocrit level. Thrombocytopenia can occasionally be cyclic, occurring at intervals of 10-25 days. During periods of thrombocytopenia, there are high thrombopoietin levels in the plasma when platelet counts are normal, thrombopoietin levels are low. Cyanotic congenital heart disease may be associated with prolonged bleeding time in spite of normal platelet counts, which is related to an impairment in platelet aggregation by adenosine diphosphate (ADP), norepinephrine, and collagen. This impairment is correlated with the severity of hypoxia. Affected children usually experience little bleeding during corrective surgery, which, if successful, results in an improved...

Clinical Presentation Of Aidsrelated Lymphoma

Patients with bone marrow involvement have a statistically increased likelihood of leptomeningeal lymphoma (42). Of interest, no specific symptom is associated with marrow involvement, and hematologic parameters are similar in the presence or absence of lymphoma, with the exception of thrombocytopenia < 100,000 DL, seen more often in patients in whom the marrow is involved (42).

Generalized Bone Marrow Disorders

All causes of constitutional aplastic anemia may present with thrombocytopenia in the newborn (see Chapter 6). Benign disease (e.g., Gaucher disease, Niemann-Pick disease, osteopetrosis Chapter 5) and malignant disease (e.g., congenital leukemia Chapter 14) can present with neonatal thrombocytopenia. Hyperglycinemia with ketosis and the closely related metabolic disorder of methyl-malonic acidemia may cause periodic thrombocytopenia, as well as neutropenia, during infancy. Infants with these metabolic disorders present with lethargy, vomiting, and ketosis during the neonatal period. A similar disorder, isovaleric acidemia, is associated with a generalized marrow hypoplasia causing thrombocytopenia and neu-tropenia. Neonatal thrombocytopenic purpura has been reported in infants born to hyperthyroid mothers. The mechanism has not been defined.

Suggested Readings

Bussell JB, Skupski DW, MacFarland JG. Fetal alloimmune thrombocytopenia concensus and controversy. The Journal of Maternal-Fetal Medicine 1996 5 281-292. Fetal alloimmune thrombocytopenia consensus and controversy. J Maternal-Fetal Med 1996 5 281-92. Heath KE, Campos-Barros A, Toren A, et al. Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant thrombocytopenias May-Hegglin anomaly and Fechtner, Sebastian, Epstein and Alport-like syndromes. Am J Hum Genet 2001 69 1033-1045. Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant thrombocytopenias May-Hegglin anomaly and Fechtner, Sebastian, Epstein, and Alport-like syndromes. Am J Hum Genet 2001 69 1033-45.

Antiphospholipid Syndrome

Antiphospholipid antibodies (aPL) are antibodies directed at phospholipids. The aPL family includes anti-cardiolipin antibodies (aCL), lupus anticoagulant (LAC) antibodies, and antibodies causing both true-and false-positive tests for syphilis. Autoimmune aPL are associated with arterial and venous thrombosis, midpregnancy fetal loss, thrombocytopenia, stroke, cardiac valvular disease, and other, less common complications. The aPL syndrome may be seen in patients with systemic lupus erythematosus (SlE) or in otherwise healthy persons (as primary antiphospholipid syndrome, or PAPS). The presence of aPL is necessary but not sufficient for the diagnosis of the aPL syndrome (APS) the syndrome requires the presence of aPL in the setting of typical complications (precise definitions vary).

Clinical complications

Hematologic manifestations are generally thrombocytopenia and hemolytic anemia which is Coombs'-positive (Evans' syndrome when these occur together). IgG aPL has been detected in up to 72 of SLE patients with thrombocytopenia and in 30 of patients with primary autoimmune thrombocytopenia. An association of aPL with microangiopathy has been reported in a number of settings, from severe preeclampsia associated with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) to a thrombotic microangiopathic hemolytic anemia.

Laboratory studies and imaging

IgM RF is detected in the serum of about 75 to 80 of RA patients. High titers are associated with more severe and extraarticular disease. The fact that 20 of RA patients are seronegative highlights the fact that the diagnosis of RA is based on clinical, not laboratory, data. An elevated erythrocyte sedimentation rate (ESR) and levels of C-reactive protein are commonly found in RA and correlate well with disease activity in most patients. Normochromic normocytic anemia of chronic disease is frequently seen in active RA it may be complicated, however, by other conditions, such as drug-induced suppression of bone marrow and blood loss. Thrombocytosis is a frequent correlate of active RA thrombocytopenia and leukopenia may be seen in drug-induced bone marrow suppression or in Felty's syndrome. Elevated alkaline phosphatase is common in severe disease, but elevation of other liver enzymes more likely is related to treatment with nonsteroidal antiinflammatory drugs...

ARecommended treatment regimen

Severe joint inflammation and deformities (20 to 30 or more red, warm, swollen, tender joints with ulnar deviation, swan neck deformities, and moderate to severe limitation in range of motion), morning stiffness lasting most of the day, loss of work, severe fatigue with weight loss, rheumatoid nodules, and possibly other extraarticular manifestations, such as sclerosis, serositis, ESR between 50 and 100 mm h with significant anemia (hemoglobin, 9.5 g ) and thrombocytosis (platelet count, 500,000 to 600, 000 mm3 or higher), many erosions, joint space narrowing, and joint deformities noted on plain radiography.

Common adverse effects include the following

Hematologic toxicity is potentially dangerous and dictates the need for close follow-up. Mandatory testing includes complete blood cell counts, including platelet count, differential counts, and definition of the absolute neutrophil count, at 2-weekly intervals for the first 6 months of therapy and at least monthly thereafter. Recording laboratory data on flow sheets will permit early detection of downward trends in white blood cell or platelet counts. Hematologic toxicity may be sudden in onset and may occur in the interval between scheduled laboratory studies. Thus, patients must be aware that they need to report the development of sore throat, skin or mucous membrane bleeding, infection, or fever. Downward trends of white blood cell and platelet counts (specifically a white cell count 3,000 mm 3 or a platelet count < 100,000 mm3) require immediate and permanent discontinuation of D-penicillamine therapy. Leukopenia associated with thrombocytopenia or thrombocytopenia alone may...

DCommon adverse effects

Dose-related bone marrow suppression with leukopenia and thrombocytopenia. d. Administration. CTX (Cytoxan) tablets are 50 mg in size. The usual oral dose begins with 50 mg d for 1 week, and then the dose is increased by 50 mg if the complete blood count is stable. The usual oral therapeutic dose is 2 mg kg daily, or 75 to 125 mg d. Higher doses may be needed in severe cases. Complete blood count, differential and platelet count, and urinalysis are assessed every 7 to 14 days initially, then every 2 to 4 weeks after 2 to 3 months of stable dosage. The IV regimen is 0.5 to 0.75 g m2 monthly. Once the patient has responded to oral and IV CTX, a switch to a less toxic DMARD, such as MTX, is appropriate to decrease the potential for oncogenicity, sterility, and other side effects. Given the renal excretion of CTX metabolites, dose adjustments and careful hematologic monitoring are needed in patients with renal insufficiency.

Clinical Features Of

The predominant physical findings were peripheral lymph node enlargement (72 ), hepatomegaly (47 ), splenomegaly (25 ), and skin lesions (53 ). Various skin lesions, such as papules, erythema, and nodules were frequently observed in ATL patients. ATL cells densely infiltrate the dermis and epidermis, forming Pautrier's microabscesses in the epidermis (Fig. 5). Hypercalcemia (50 ) was frequently associated with ATL. Other findings at onset of the disease were abdominal pain, diarrhea, pleural effusion, ascites, cough, sputum, and an abnormal shadow on chest X-ray films. The white blood cell count ranged from normal to 500 x 109 L. Leukemic cells resembled Sezary cells, having indented or lobulated nuclei. The typical surface phenotype of ATL cells characterized by monoclonal antibodies was CD3+, CD4+, CD8-, and CD25+. Anemia and thrombocytopenia were rare. Eosinophilia was frequently observed in ATL patients as well as in those with other T-cell malignancies (64). Cytokines, such as...

Routine laboratory examination may reveal abnormalities 1 Hematology

Anti-platelet antibodies have been demonstrated by a direct test similar to Coombs' test. B. Organ systems that may be affected by SLE include skin and mucous membranes (rash, ulceration, alopecia), joints (nondeforming, often symmetric polyarthritis and periarthritis), kidneys (glomerulonephritis), serosal membranes (pleuritis, pericarditis, abdominal serositis), blood (hemolytic anemia, leukopenia, thrombocytopenia), lungs (transient infiltrates, rarely progressive hemorrhagic pneumonitis), and nervous system (seizures, strokes, psychosis, peripheral neuropathies).

Chediakhigashi Syndrome

This is another X-linked primary immune deficiency. The clinical manifestations of the disease include impaired T-cell function and a low platelet count. (Platelets are involved in blood clotting.) Patients usually present with frequent bleeding problems and infections. The gene that, when defective, causes this disease codes for a protein that is important in helping cells of the immune system react properly to activating signals. For example, T cells in WAS patients can recognize a peptide class I MHC signal at a dendritic cell surface, but they cannot easily translate this signal into activation of the T cell. This same basic defect also impairs B-cell activation and NK cell function. Affected children can be managed by treating each of the clinical problems as they arise. In severe cases, a bone marrow transplant, to replace defective cells with normal ones, may be tried. As we will discuss below, this is a risky procedure generally used only when it is felt a patient is at great...

Hematologic abnormalities

Immune thrombocytopenia secondary to SLE usually responds to corticosteroid therapy. Platelet counts of 80,000 to 100,000 are considered adequate. Life-threatening thrombocytopenia unresponsive to several weeks of 60 mg of prednisone daily may improve with gamma globulin therapy (400 mg kg IV daily for 5 days consecutively), which usually leads to an immediate (2 to 3 days) rise in the platelet count. Danazol, azathioprine, vincristine, vinca alkaloid-loaded platelets, and IV pulse cyclophosphamide have been used on occasions for steroid-resistant thrombocytopenia.

ADP Antagonists Ticlopidine and Clopidogrel

There are several important differences in the pharmacokinetics and pharmacodynamics of the currently available GP IIb IIIa inhibitors. Abciximab has a very high affinity for GP IIb IIIa and a long half-life (8-12 h), and after discontinuation of the infusion, platelet function returns gradually. In contrast, the small-molecule inhibitors eptifibatide and tirofiban have short half-lives, and platelet function returns quickly after discontinuation of the infusion. Although it has high affinity, abciximab has low specificity and binds to other integrins, including the vitronectin receptor (GP aVb3), which is found on endothelial cells. Whether this is of clinical relevance remains unknown. In contrast, eptifibatide and tirofiban are extremely specific for the GP IIb IIIa receptor. In addition to the expected side effect of excess bleeding, abciximab has also been associated with profound thrombocytopenia in 0.5-1.0 of cases (79) and the development of anti-mouse antibodies in 5-6 of...

Pathogenesis and Clinical Features

Like the alphaviruses, flaviviruses may cause encephalitis or a fever arthritis rash syndrome, the pathogenesis and clinical features of which were described in Chapter 25, but yellow fever and dengue viruses as well as a number of tick-borne flaviviruses cause hemorrhagic fever. The striking feature of this potentially lethal syndrome is hemorrhage, which manifests as pefechiae and ecchymoses on the skin and mucous membranes (see Fig. 33-4), with bleeding from any or all of the body orifices. Examination of the blood reveals thrombocytopenia and usually leukopenia. In fatal cases the patient collapses abruptly from hypotensive shock Further details are given in Chapters 30, 32, 33, and 36.

Haematological and biochemical findings

Anaemia is normocytic and may be severe (haemoglobin < 4 g dl). Thrombocytopenia (< 100 000 platelets pl) is usually present, and peripheral leukocytosis is found in patients with the most severe disease. Elevation of serum creatinine, bilirubin and enzymes, e.g. aminotransferases and 5'-nucleotidase, may be found. Levels of liver enzymes are much lower than in acute viral hepatitis. Severely ill patients are commonly acidotic, with low capillary plasma pH and bicarbonate concentrations. Fluid and electrolyte disturbances (sodium, potassium, chloride, calcium and phosphate) are variable. Concentrations of lactic acid in the blood and cerebrospinal fluid are often high in both adults and children, in proportion to the severity of the disease.

Wiskottaldrich Syndrome

The severity of this X-linked disorder increases with age and usually results in fatal infection or lymphoid malignancy. Initially, T and B lymphocytes are present in normal numbers. WAS first manifests itself by defective responses to bacterial polysaccharides and by lower-than-average IgM levels. Other responses and effector mechanisms are normal in the early stages of the syndrome. As the WAS sufferer ages, there are recurrent bacterial infections and a gradual loss of humoral and cellular responses. The syndrome includes thrombocytopenia (lowered platelet count the existing platelets are smaller than usual and have a short half-life), which may lead to fatal bleeding. Eczema (skin rashes) in varying degrees of severity may also occur, usually beginning around one year of age. The defect in WAS has been mapped to the short arm of the X chromosome (see Table 19-1 and Figure 19-2) and involves a cytoskeletal glycoprotein present in lymphoid cells called sialophorin (CD43). The WAS...

Functional Status Complications and Causes of Death

Major causes of death from cancer include infection, organ failure, carcinomatosis, and hemorrhage. Infections may be the common causes of pneumonia or caused by gram negative bacilli such as Escherichia coli, Klebsiella species, and Pseudomonas aeruginosa, and fungi such as Aspergillus or Candida species. Dysfunction of the respiratory, cardiac, hepatic, renal, or central nervous system leads to organ failure. Thromboses in the lung, heart, mesenteric arteries, or brain may also cause death. Carcinomatosis associated with advanced metastatic disease can be clinically undetected, but autopsy may reveal extensive invasion of vital organs. Hemorrhage, secondary to thrombocytopenia (abnormally low platelet count), or invasion of major blood vessels occur in the GI tract, lungs, and brain. As a result of multiple combined complications and metabolic derangements in patients with advanced metastatic disease, it is often not possible to establish an immediate single cause of death.

Diseases Caused by Arenaviruses

For example, Lassa virus produces some focal necrosis of the liver, interstitial pneumonitis, facial edema, and encephalopathy, but death is attributable to the sudden onset of hypovolemic shock in the second week of the illness. The pathophysiology of the hemorrhagic fever shock syndrome is not fully understood. One major point of difference from hemorrhagic fevers caused by viruses of other families is that disseminated intravascular coagulation does not appear to play a significant role until perhaps the terminal phase of the illness. In Lassa fever it appears that an inhibitor of platelet function may be responsible for the bleeding and perhaps also for endothelial dysfunction. Bleeding with severe thrombocytopenia is more prominent in Junin and Machupo viral hemorrhagic fevers.

Systemic lupus erythematosus and scleroderma

In general, a diagnosis of clinical SLE should not prompt a search for occult malignancy. However, lupuslike serology and unexplained Coombs'-positive anemia, thrombocytopenia, or circulating anticoagulants without clinical features of SLE warrant consideration of an occult neoplasm. In addition, in a patient with a known tumor who presents with pleural effusions, pericarditis, or nondeforming polyarthritis, an associated lupuslike illness should be considered.

Lowmolecularweight Heparin

LMWH has several clear advantages over UFH. First, its effective half-life is approx 4 h, which allows twice daily dosing. Because it does not bind to plasma proteins, such as platelet factor four and von Willebrand factor, it cannot be neutralized, and its anticoagulant response is much less erratic than that of UFH. Therefore, laboratory monitoring is not required. Furthermore, LMWH remains active in a platelet-rich environment because it can bind platelet-bound factor Xa. Unlike UFH, it does not increase vascular permeability and inhibit platelet function (30,31). Finally, heparin-induced thrombocytopenia occurs much less frequently with LMWH than with UFH (30,33).

South American Arenavirus Hemorrhagic Fevers

Argentine hemorrhagic fever is a more typical hemorrhagic fever than Lassa fever. The pathology is largely confined to the circulatory system. There is relalively little inflammation or necrosis prominent features are hemorrhage, thrombocytopenia, leukopenia, hemoconcentration, proteinuria, and hypotension, sometimes culminating in death from hypovolemic shock.


Heparin preparations are contraindicated in patients with known hypersensitivity to the drug, active bleeding (except when caused by disseminated intravascular coagulation), hemorrhagic disorders, severe thrombocytopenia, or recent surgery (except for the LMWHs used after certain surgical procedures to prevent thromboembolic complications) and during pregnancy (Pregnancy Category C). The LMWHs are contraindicated in patients with a hypersensitivity to the drug, heparin, or pork products and inpatients with active bleeding or thrombocytopenia.

LMWH and Percutaneous Coronary Intervention

Tion of abciximab and reduced dose enoxaparin was associated with a low incidence of bleeding or ischemic events. Major and minor bleeding occurred in 1.1 and 6.2 of NICE 1 patients and 0.4 and 7.0 of NICE 4 patients, respectively, at 30 d post-PCI. There was a low incidence of thrombocytopenia with only 0.9 and 2.1 of NICE 1 and NICE 4 patients having a platelet count less than 100,000 at 30 d. The composite end point of death, MI, and urgent revascularization in-hospital (Fig. 3) and at 30 d post-PCI was 6.2 and 7.7 in NICE 1 patients and 6.5 and 6.8 in NICE 4 patients, respectively. Anticoagulant activity measured at 5 and 15 min post-enoxaparin bolus reflected values expected for 1.0 and 0.75 mg kg enoxaparin treatment, while no differences occurred at 4 and 8 h. The conclusion from these studies is that enoxaparin (1.0 mg kg) without abciximab, as well as enoxaparin (0.75 mg kg) in combination with abciximab, provides safe and efficacious anticoagulation during PCI. Subsequently,...

Clinical Features

Crimean-Congo hemorrhagic fever commences abruptly with fever, headache, and severe back and abdominal pain, and progresses to extensive hemorrhages from almost any site, with melena, hematemesis, hematuria, and a hemorrhagic skin rash (Fig. 33-4). Leukopenia, thrombocytopenia, proteinuria, and hepatitis are key findings. Blood loss from internal bleeding leads to shock, pulmonary edema, and death. Case-fatality rates range from 5 to 50 , depending on the availability of modern medical care.

Specific clinical problems

Hematologic abnormalities such as transient thrombocytopenia are commonly seen. Frank adult respiratory distress syndrome may develop and become life-threatening. Treatment includes the administration of increased concentrations of inspired oxygen (possibly intubation), prevention of pulmonary hypertension by fluid restriction, use of diuretics and venodilators, and prevention of pain. The use of corticosteroid therapy is not recommended. In high-risk circumstances (i.e., patients undergoing bilateral total joint arthroplasty, those with preexisting cardiopulmonary dysfunction), pulmonary artery catheterization for 24 to 48 hours can be helpful to guide therapy. If the pulmonary artery diastolic pressure is maintained at below 20 mm Hg, respiratory insufficiency is usually prevented.

Phase I and Pharmacokinetic Studies

Hematologic responses, defined as a 50 decrease in the WBC from baseline, maintained for at least 2 weeks, were achieved in all patients treated with 140 mg or greater of imatinib. Once doses of 300 mg or greater were reached, 53 54 patients (98 ) achieved a complete hematological response (CHR), defined as a normal WBC and platelet count with no circulating immature myeloid cells, maintained for at least 4 weeks (Druker et al. 2001b). Lowering of the WBC was typically seen within the first 2-3 weeks of therapy with achievement of normal WBCs in 3-6 weeks. Normal WBCs were maintained in 51 of 53 patients with a median duration of follow-up of 310 days. At doses of imatinib of exceeding or equal to 300 mg, cytogenetic

Safety and Tolerability

Imatinib has generally been well tolerated, with grade 3 or 4 nonhematologic toxicities being uncommon. The most common grade 1 or 2 toxicities include fluid retention, nausea, muscle cramps, skin rashes, fatigue, and diarrhea. Myelosuppression is more common in advanced phase patients than in chronic phase patients, and imatinib induced prolonged aplasia in 1 of blast crisis patients (Sawyers et al. 2002). In contrast, patients with GIST treated with 400 or 600 mg per day of imatinib had rates of grade 3 4 neutropenia and thrombocytopenia of 5 and less than 1 , respectively, demonstrating the specificity of this side effect to leukemia patients (Demetri et al. 2002). Thus, myelosuppression is more likely to be due to suppression of the BCR-ABL-positive clone as opposed to inhibition of normal hematopoiesis. For this reason, it is not clear how much is accomplished by dose reduction for myelosuppression.

Blood Component Therapy

The problem of refractoriness applies particularly to platelet transfusions. Patients who are refractory show no rise or significantly less than the expected rise in platelet count following a platelet transfusion. In some patients, refractoriness occurs much sooner than in others. Specific factors affecting platelet survival will be discussed in the section on platelet transfusions. 4. Blood loss due to thrombocytopenia The causes of thrombocytopenia in children who have cancer are 1. The platelet count is less than 15,000-20,000 mm3. 2. The platelet count is greater than 20,000 mm3, but the patient is bleeding (e.g., prolonged epistaxis, GI bleeding, or CNS bleeding). 3. The patient is scheduled for an invasive procedure and the platelet count is less than 50,000 mm3. The dose of platelets given per transfusion is 1 unit random-donor platelets 10 kg or 1 unit single-donor platelets 50 kg. Apheresis units may be divided for smaller patients. Use ABO-type-specific platelets. The...

Systemic IL10 as a Therapy for Crohns Disease

Fedorak et al report a 24 week double blind placebo controlled study of 95 patients with moderately active Crohn's disease who were not concurrently receiving steroid, mesalasine or other immunosuppressive therapy. Patients were randomized to receive subcutaneous rhuIL-10 at one of four doses (1, 5, 10, and 20 g kg) or placebo daily for 28 days. During the 20-week follow period a dose dependent, but fully reversible, anemia and thrombocytopenia were noticed. At the end of the treatment period 23.5 of patients receiving 5 g kg rhuIL-10 (n 17) experienced clinical remission and endoscopic improvement compared to 0 of patients receiving placebo (n 23). Interestingly higher doses were less effective, although there was no difference in reported adverse events between doses. During the course of the 20-week follow period disease recurrence requiring therapeutic intervention occurred in 70 of placebo treated patients compared to 55 of the rhuIL-10 treated group.43

Viral Hemorrhagic Fevers

Although not an entirely homogeneous group of diseases, the hemorrhagic fevers (Table 36-5) share the common characteristic of widespread hemorrhage from the body's epithelial surfaces, including internal mucosae such as the gastrointestinal tract as well as the skin. The skin rash is often a mixture of pinpoint hemorrhages (petechiae) and massive bruising (ecchymoses), as depicted in Fig. 36-5B. The pathogenesis of these important diseases is generally not well understood. Thrombocytopenia and leukopenia are almost always present, but no general mechanism has been discovered to explain the hypovolemic shock without major blood loss which may lead to death within hours in dengue or Lassa fever, for example. Severe liver damage, extensive bleeding, and disseminated intravascular coagulation may be the key to the high mortality in the African hemorrhagic fevers, Crimean hemorrhagic fever, and the hemorrhagic form of Rift Valley fever. Encephalopathy and or pneumonia can also be...

Transient Erythroblastopenia

White blood cell and platelet count are usually normal. Note, however, that approximately 10 of patients may have significant neutropenia (absolute neutrophil count ANC , < 1000 mm3) and 5 have thrombocytopenia (platelet count, < 100,000 mm3). (Table 6-3 lists the hematologic characteristics.) An analysis of 50 patients presenting with TEC at our institution revealed a high incidence of neutropenia (64 with an ANC of < 1500 mm3).

There Is An Intercalary Defect In Tar Consisting Of Absent Radii With Normal Thumbs Whereas In Fa The Defect Is

Hematologic dysfunction usually presents with macrocytosis, followed by thrombocytopenia, often leading to progressive pancytopenia and severe aplastic anemia (SAA). FA frequently terminates in MDS and or AML. 1. The differential diagnosis of FA generally includes acquired aplastic anemia, congenital amegakaryocytic thrombocytopenia (CAT), TAR syndrome as well as VATER VACTRL (vertebral anomalies, anal atresia, cardiac anomalies, tracheoesophageal fistula, renal anomalies, limb anomalies) syndromes. FA is easily distinguished from TAR syndrome (Table 6-12). There is an intercalary defect in TAR consisting of absent radii with normal thumbs, whereas in FA the defect is terminal, an abnormal radius always being associated with anomalies of the thumb. FA testing is warranted in any child who presents with hemato-logic cytopenias, unexplained macrocytosis, aplastic anemia or AML, as well as representative congenital abnormalities or solid tumors typical of FA such as head and neck,...

Clinical Presentation and Evaluation

Clinically, PPHN is most often recognized in term or near term neonates, but clearly can occur in premature neonates as well (Table 1). PPHN is often associated with perinatal distress (e.g., asphyxia, low APGAR scores, meconium staining) however, idiopathic PPHN can lack signs of acute perinatal distress. PPHN often presents as respiratory distress and cyanosis within 6-12 hrs of birth. Laboratory findings include low glucose, hypocalcemia, hypothermia, polycythemia or thrombocytopenia. Radiographic findings are variable, depending upon the primary disease asociated with PPHN. Classically, the chest x-ray in idiopathic PPHN is oligemic, may appear slightly hyperinflated, and lacks parenchymal infiltrates. In general, the degree of hypoxemia is often disproportionate to the severity of radiographic evidence of lung disease.

Isolated angiitis of the central nervous systen is a recently recognized vasculitic disorder primarily involving the

The classic triad is palpable purpura with a normal platelet count, colicky abdominal pain, and arthritis. Palpable purpura occurs in 100 of patients but is the presenting symptom in only half. Dependent areas are usually involved, and involvement of the buttocks is common. Arthritis is transient and usually involves the knees and ankles there are no permanent sequelae. Up to one-third of patients may experience hemoptysis and half have occult gastrointestinal bleeding, but serious hemorrhage is rare. Ten percent to fifty percent have renal involvement, ranging from transient isolated microscopic hematuria to rapidly progressive glomerulonephritis. HSP and immunoglobulin A (IgA) nephropathy are similar, but the latter is confined to the kidney, whereas the former is a systemic disease. B. Myxomas are benign cardiac tumors, most commonly found in the left atrium. They can cause extracardiac symptoms of petechial skin rashes, Raynaud's phenomenon,...

Decreased or Absent Megakaryocytes in the Marrow

Amegakaryocytic Thrombocytopenia A variety of syndromes have been described that have in common a primary impairment of platelet production as the major cause of thrombocytopenia. Bone marrow examination usually reveals decreased numbers of megakaryocytes. This may be isolated megakaryocytic hypoplasia or part of a generalized bone marrow disease, such as aplasia of the marrow or infiltration of the marrow by nonneoplastic or neoplastic disease. Characteristics of congenital thrombocytopenic syndromes are listed in Table 10-9. Congenital Amegakaryocytic Thrombocytopenia without Anomalies Isolated thrombocytopenia and megakaryocytic hypoplasia without any congenital anomalies has been reported. Patients present at a median age of 7 days. Of a series of 26 patients, 11 developed aplastic anemia at a median age of 3 years. One patient developed AML and one developed MDS. The median survival was 6 years. This is an autosomal recessive disorder due to a homozygous or compound heterozygous...

Hemolytic Uremic Syndrome

Hemolytic uremic syndrome (HUS) is associated with acute hemolytic anemia, thrombocytopenia, and renal failure in infants and young children (between 6 months and 5 years of age). Thrombocytopenia Life-threatening bleeding due to thrombocytopenia is uncommon. Platelet transfusions can worsen thrombotic complications of the illness and should not be given to a patient with HUS.

Azathioprine Imuran and 6Mercaptopurine Purinethol

Hematologic toxicity is usually mild leukopenia and thrombocytopenia aplastic anemia is rare. Drug fever may occur. Hepatitis and pancreatitis may also occur. Nausea, especially during initiation of therapy, is common. Stomatitis may be seen. An increased incidence of late lymphoreticular and hematopoietic malignancy is possible. The immunosuppressive effects of these drugs increases susceptibility to infections. Complete blood cell counts and platelet counts should be obtained initially weekly and then monthly. A rapid fall in leukocyte count requires a decrease in dosage or discontinuation of the drug. Liver function tests should be performed periodically. Allopurinol inhibits the metabolism of both AZA and 6-MP, which causes high levels to accumulate thus, concomitant use of allopurinol should be avoided, or else a significant reduction in the AZA dose by 75 is appropriate. AZA has been used safely in pregnancy, but as with any medication, discontinuation of the drug, if possible,...

Platelet concentrates

Platelet transfusions are used to prevent spontaneous bleeding or to stop bleeding in patients with established thrombocytopenia or platelet dysfunction e.g. hypoplastic anaemia or bone marrow failure due to replacement with malignant cells or to the effects of chemotherapy.

Subacute Or Chronic Meningitis

Fungal meningitis is commonly present in a state of immunosuppression which is also often associated with thrombocytopenia hence platelet counts should be per formed prior to performing a lumbar puncture. If the platelet count is < 50,000 mm3, platelet transfusion is necessary. Neuroimaging (CT or MRI scan), preferably with contrast, should also be performed in these patients, as fungal meningitis is often associated with intracranial mass lesions. Fungi are typically difficult to isolate and culture from the CSF, because the infection occurs primarily in the basilar cisterns, and fungi are seldom present in the lumbar thecal sac where the lumbar puncture is performed. Hence large volumes (40-50 mL) of CSF are typically necessary for fungal cultures, and to improve the chances of finding the organism, the CSF from the later tubes should be used and it should be centrifuged and the pellet used for cultures and smears. If repeated cultures are negative and it remains essential to...

Anticoagulation Coagulation Cascade

Antithrombin Site Action

Heparin-induced thrombocytopenia (HIT) is a well-documented complication of heparin administration (20). HIT type I occurs in approx 10 of patients receiving heparin and is manifested by mild thrombocytopenia occurring within 48 h of the initiation of therapy. The platelet count rarely falls below 100,000 mm3 and returns to normal within 5 d even if heparin therapy is continued. The mechanism is thought to be direct heparin-mediated platelet aggregation. Patients with HIT type I do not go on to have thrombotic complications. In contrast, HIT type II is marked by more severe thrombocytopenia and a greatly increased risk of thrombosis. This syndrome occurs in 1-5 of patients receiving heparin, approximately one-third of whom will go on to develop thrombosis. The platelet count usually starts to decrease after 5-12 d of therapy (and potentially earlier if the patient has been exposed to heparin before) and usually falls by more than 50 or drops to less than 100,000 mm3. If heparin is...

Ovarian Hyperstimulation Syndrome

Hypovolemia and hemoconcentration need immediate corrections. When necessary, intravenous crystalloid infusion or plasma expanders are given to maintain central venous pressure. Replacement may require central venous pressure monitoring. Diuretics should not be given with, as the fluids in the abdominal and thoracic cavity are not responsive to diuretics and the further intravascular depletion can cause hypotension, shock, and thrombosis. Administration of low-dose heparin to prevent thromboembolism needs to be balanced against the risk of ovarian bleeding, possible need for paracentesis, and the possibility of heparian-induced thrombocytopenia. Most of our hospitalized patients are commenced on heparin 5000 U x 2 day subcutaneously on admission and reviewed after 24 hr. Heparin should be continued until discharge from the hospital if the patient has risk factors or past history of thrombosis, family history of thromboembolism, smoking, obesity, or varicose veins. Heparin should also...

Pathogenic Organisms Are Inactivated by Heat or Chemical Treatment

Attenuated Killed Dna Vaccine

Thrombocytopenia Death Although there have been several reports of thrombocytopenia occurring after measles including bleeding, the risk has not been properly quantified. This risk has been reported after MMR vaccination and cannot only be attributed to the measles component. MMR measles, mumps, and rubella. SSPE subacute sclerosing panencephalitis.

Familial Eosinophilia

Familial eosinophilia is an autosomal dominant disorder. A genome-wide search showed evidence of linkage on chromosome 5q31-33 between markers D55642 and D55816. Some of the affected members are found to have high WBC counts, lower RBC counts, intermittent thrombocytopenia, cellular infiltration with mast cells in the liver and bone marrow, or involvement of the heart and nervous system. The levels of IL-3, IL-5, and GM-CSF are normal.

Tumor Immunology 341 Hematopoiesis

Adult erythrocytes have no nucleus, are biconcave in shape, and contain hemoglobin ( 15 mg mL blood), the iron-containing red pigment that is responsible for the transport of oxygen. Erythrocytes live for approximately four months after which they are destroyed by the spleen. Late stage cancers are often accompanied by anemia (< 4 x 106 cells L blood) because of a complex set of factors including decreased production of red cells and or iron deficiency. Platelets which have a life span of 8 days and a normal count of 150,000 to 350,000 per L assist in the blood clotting cascade. A marked increase in the number of platelets (thrombocytosis) is associated with the early stages of certain leukemias. A marked decrease of the platelet count (thrombocytopenia, < 10,000 plate-lets L blood) may occur from chemotherapy or radiation therapy resulting in bleeding in certain hematologic malignancies.

Immune Idiopathic Thrombocytopenic Purpura

Thrombocytopenia (platelet count less than 100,000 mm3) This condition may be acute, chronic, or recurrent. In the acute form, the platelet count returns to normal (> 150,000 mm3) within 6 months after diagnosis, and relapse does not occur. In the chronic form, the platelet count remains low beyond 6 months. In the recurrent form, the platelet count decreases after having returned to normal levels. In adults, the chronic form is more common, whereas in children, the acute form is more common. The clinical features of acute and chronic ITP are listed in Table 10-3. I. Increased platelet destruction (normal or increased megakaryocytes in the marrow megakaryocytic thrombocytopenia) A. Immune thrombocytopenias 3. Neonatal immune thrombocytopenias a. Neonatal autoimmune thrombocytopenia b. Neonatal alloimmune thrombocytopenia B. Nonimmune thrombocytopenias III. Decreased platelet production deficient thrombopoiesis (decreased or absent megakaryocytes in the marrow amegakaryocytic...

The dosage is 100 mg twice daily Mycophenolate Mofetil Cell Cept

Pruritus and skin rash represent the most common side effects and can occur at any time. They can be treated by either lowering the dosage or administering antihistamines. If necessary, the therapy may be interrupted until the rash resolves. Stomatitis also occurs. Alteration of taste is frequent, independent of dosage, and self-limited, with resolution in 2 to 3 months despite continued drug administration. Bone marrow depression may occur precipitously at any time. If the platelet count falls below 80,000 to 100,000, therapy must be discontinued. The most common late toxic effect is immune complex nephropathy. Proteinuria may be seen in 20 of patients. If proteinuria exceeds 1 g d, the dosage should be reduced. Nephrotic syndrome, hypoalbuminemia, or hematuria requires discontinuation of the drug. Less common side effects include autoimmune syndromes (lupus syndromes, Goodpasture's syndrome, myasthenia gravis, pemphigus, stenosing alveolitis, polymyositis), which necessitate prompt...

Nonimmune Hemolytic Anemia

The blood smear is characterized by the presence of burr erythrocytes, schistocytes, helmet cells, and microspherocytes. This occurs in association with evidence of hemolysis and usually, but not invariably, thrombocytopenia. The severity of both the anemia and the thrombocytopenia, as well as the degree of compensatory ery-throid response, varies greatly. Intravascular hemolysis occurs in all forms plasma hemoglobin levels may be elevated, haptoglobin absent, hemosiderinuria present, and urinary iron excretion increased in the more chronic forms. Elevated serum fibrin degradation products in some cases of MAHA may represent evidence of associated DIC. The thrombocytopenia is due to consumption of platelets in the microthrombi and is an example of excessive platelet destruction rather than a failure of production. The marrow, therefore, shows normal numbers of megakaryocytes together with erythroid hyperplasia. Acute forms of MAHA are sometimes accompanied by disseminated...

Juvenile Myelomonocytic Leukemia

Blastic Bone Metastases

WBC count The majority of patients have > 25,000 mm3 WBC counts. Monocytosis may be present for months before overt symptoms of JMML appear. Thrombocytopenia can present with hepatosplenomegaly, lymphadenopathy, leukocytosis, thrombocytopenia, and elevated hemoglobin F levels. The following tests are useful The inhibitory effect of TNF-a on normal hematopoiesis causes bone marrow suppression and results in anemia and thrombocytopenia. Splenomegaly also contributes to the development of anemia and thrombocytopenia. IL-1 stimulates accessory cells to produce more GM-CSF. Platelet count below 33,000 mm3 at diagnosis (considered to be the strongest indicator of prognosis).

Platelet Pathophysiology In Arterial Thrombosis

Platelets are the smallest of blood cells, with an average diameter of 1-2 im and a mean cell volume of 5-6 fL, and have a life span of approx 7-10 d (9), which apparently is not reduced in activated platelets (10). The average platelet count is quite high, ranging from 140-440 X 109 L (11). Therefore, even seemingly subtle changes related to the function and activation status of platelets may have a significant impact on physiologic or pathologic processes.

Systemic Sclerosis and Related Syndromes

Before the introduction of angiotensin-converting enzyme (ACE) inhibitors, hypertensive renal crisis was a major cause of mortality in patients with diffuse scleroderma. This syndrome is characterized by a hyperreninemic state with accelerated hypertension, rapidly progressive azotemia, microangiopathic hemolysis, and consumptive thrombocytopenia. Urinalysis reveals evidence of protein and red blood cells. In the absence of appropriate diagnosis and therapy, severe complications, including hypertensive retinopathy, encephalopathy, and renal failure, can ensue. In some patients, normotensive renal crisis can occur, and this may be associated with corticosteroid use. In a patient in whom scleroderma has been diagnosed, particularly a patient with rapidly progressive, diffuse disease, regular blood pressure monitoring is essential, and daily self-monitoring of blood pressure at home is advisable.

No inflammation present

Neoplastic disorders associated with infiltration of the bone marrow include leukemia, lymphoma, and neuroblastoma. All may present with difficulty walking or joint pains. Disproportionate anemia, thrombocytopenia, hyperuricemia, lymphadenopathy, or hepatosplenomegaly should prompt further investigation and bone marrow aspiration.

Metabolic and Endocrine Emergencies

Initial white cell count is greater than 100,000 mm3 Because of the volume of blood required to prime the pump, leukopheresis is usually used for children > 4 years of age Transfuse platelets to keep platelet count over 20,000 mm3 to decrease the risk of intracranial hemorrhage. Avoid packed RBC transfusions, because it will increase the viscosity. Maintain hemoglobin less than 10 g dL. Started when patient is stabilized and has adequate urine output

Anaphylactoid Purpura

Henoch-Schonlein purpura is nonthrombocytopenic vascular purpura. The pur-puric eruption differs considerably from that due to thrombocytopenia in that lesions are maculopapular, initially resembling urticaria because of edema and perivascular infiltration and later becoming erythematous, with central areas of hemorrhage that finally fade to brown because of denaturation of the extravasated hemoglobin. The rash appears on the buttocks and on the extensor surfaces of the arms and lower legs. Accompanying the rash are joint or gastrointestinal symptoms, localized areas of edema, and renal damage. Initial hematuria occurs in about one third of patients. The platelet count, bleeding time, and tests for hemostasis are normal. A positive tourniquet test is found in 25 of patients. Treatment is symptomatic. When severe abdominal pain is present, steroid therapy is beneficial.

Diagnosis And Management

Controversies regarding anticoagulation in pregnant women arise mainly from concerns about safety to the mother vs potential damage to the fetus. Coumarin derivatives cross the placenta and can cause an embryopathy, which consists of nasal hypoplasia and or stippled epiphyses after exposure during the first trimester, and CNS abnormalities after exposure during any trimester (80). Heparin does not cross the placenta and is safe to the fetus, but prolonged heparin use causes osteoporosis a reduction in bone density is reported in up to one-third of women who receive heparin (81). Low mol-wt heparins (LMWH) also do not cross the placenta and have benefits over unfractionated heparin, such as longer half-life, more predictable dose-response, and a decreased risk of heparin-induced thrombocytopenia (82,83). A recent study showed LMWH to be safe and effective when used in 61 pregnant women at risk of embolic events, although concerns about bone density were raised in this study (83).


Some experts recommend needle biopsy under imaging guidance partly because lymphoma and nonmalignant lesions can masquerade as HCC 13 . Tissue diagnosis, however, is neither always necessary nor feasible. Biopsies entail some risk. Patients with HCC often have end-stage cirrhosis with coagulopathy, thrombocytopenia, or ascites, all of which increase the risk of bleeding. Small tumors may be difficult to reach by percutaneous biopsy. Cancer cells can rarely seed along the biopsy needle track. Earlier large studies reported a risk of about 0.003 to 0.009 of seeding 14 , but more recent studies report a 1 to 2 risk 15,16 . In some studies, the false-negative rate of biopsies is as high as 10 to 40 , particularly for small tumors, because of inadequate samples or sampling error 15,16 . The histo-pathologic criterion separating dysplastic regenerative nodules from malignancy can be ambiguous. Repeat biopsy does not significantly decrease the false-negative rate 13,16 .

Bone Marrow Failure

Table 6-2 lists the inherited bone marrow failure syndromes with their known and presumed genes. The inherited bone marrow failure syndromes had usually been divided into those resulting in pancytopenia (Fanconi anemia and dyskeratosis con-genita) and those apparently restricted to a single hematopoietic lineage (Diamond-Blackfan anemia, congenital neutropenia Kostmann syndrome, cyclic neutropenia, Shwachman Diamond syndrome , congenital amegakaryocytic thrombocytopenia, and thrombocytopenia absent radii TAR syndrome). However, it has become evident that most of these single-cell cytopenias may manifest abnormalities in other hematopoietic cell lines for example, in Shwachman Diamond syndrome and congenital amegakaryocytic thrombocytopenia, pancytopenia is fairly common (Table 6-1).


Congenital amegakaryocytic thrombocytopenia Thrombocytopenia absent radii (TAR) syndrome Shwachman Diamond syndrome (predominantly neutropenia)a Congenital amegakaryocytic thrombocytopenia (predominantly thrombocytopenia)a Diamond-Blackfan anemia (predominantly anemia)a Aplastic anemia with constitutional chromosomal abnormalities Dubowitz syndrome (congenital abnormalities, mental retardation, aplastic anemia) Acquired Idiopathic


Hematopoietic stem cell transplantation Although somewhat controversial, HLA-matched sibling donor transplantation should be considered for any patient with DBA. Consideration should be given to the fact that 20 of all patients attain remission, balanced by the risk of hematologic malignancy, myelodys-plasia, or severe aplastic anemia. A family marrow donor must be tested for the presence of a silent phenotype. Matched unrelated or incompletely matched related donor transplants have proven to be very risky and should be reserved for patients with leukemia, MDS, severe aplastic anemia, or clinically significant neutropenia or thrombocytopenia.


Severe aplastic anemia is defined as a bone marrow cellularity of less than 25 and at least two of the following findings granulocyte count, < 500 mm3 (< 200 mm3 in very severe aplastic anemia) platelet count, < 20,000 mm3 and reticulocyte count, < 40,000 mm3. The definition of mild and moderate aplastic anemia varies among researchers and institutions.

Patient Preparation

Percutaneous spine biopsy can be performed either on an inpatient or outpatient basis. The patient must not eat or drink for a minimum of 8 hours prior to the procedure. The following laboratory parameters are assessed at our institution hematocrit, hemoglobin, platelet count, prothrombin time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), blood urea nitrogen (BUN), and creati-nine. Patient allergies are recorded, with particular attention to anesthetic agents and imaging contrast agents. Prior to performing the

Invasion of Skin

A lasting local dilation of .subpapillary dermal blood vessels produces a macule, which becomes a papule if there is also edema and infiltration of cells into the area. Primary involvement of the epidermis ot separation of epidermis from dermis by fluid pressure results in vesiculation. Erosion or sloughing of the epithelium results in ulceration and scabbing, but prior to ulceration a vesicle may be converted to a pustule by polymorphonuclear cell infiltration. More severe involvement of the dermal vessels may lead to petechial or hemorrhagic rashes, although coagulation defects and thrombocytopenia may also be important in the genesis of such lesions.


Thrombocytosis is a platelet count that is more than two standard deviations above the mean. Most thrombocytosis seen in children is secondary to inflammation. Iron-deficiency anemia, major trauma, or surgery are also associated with thrombocytosis. In reactive thrombocytosis, therapy to decrease platelet count is not indicated. Because one third of the platelets are sequestered in the spleen, individuals with functional asplenia or postsplenectomy have elevated platelet counts. Postsplenectomy thrombocytosis with counts in excess of 1,000,000 mm3 is common during the immediate postsplenectomy period. Thromboembolism from this cause is rare in children. ASA, 80 mg every other day, should be given to postsplenectomy patients with marked thrombocytosis to prevent the formation of platelet thrombi. Automated platelet counts may be spuriously elevated due to microspherocytes, red

Lupus Pregnancy

Normal pregnancy may be associated with palmar and facial erythema, chloasma gravidarum, anemia, mild thrombocytopenia, edema, and an increased erythrocyte sedimentation rate. Pregnancy-induced toxemia may present with hypertension, renal insufficiency, proteinuria, generalized edema, marked thrombocytopenia, disseminated intravascular coagulation, and seizures. Eclampsia may also be associated with decreased complement levels. Changes felt to represent SLE activity and not pregnancy include an increase in anti-double-stranded DNA antibody level, lymphadenopathy, true lupus rash, inflammatory arthritis, fever, and renal sediment abnormalities of microscopic hematuria with erythrocyte casts. A. Antiphospholipid antibodies. The primary complication of aPL is fetal loss or premature delivery with fetal distress. aPL appear to act on the placenta rather than on the fetus itself, although antibody does cross the placental barrier and several case reports describe thrombotic complications...


Interferons are not effective by mouth, therefore are injected. IFN-a is much more active in vivo than IFN-p or IFN--y, probably because the latter do not achieve or maintain the required blood levels after intramuscular administration. Toxic side effects are regularly observed and may be marked with doses in excess of 107 units per day, even when highly purified cloned IFN subtypes are employed. Fever regularly occurs at high dosage but lasts only a day or so. Severe fatigue is the most debilitating symptom and may be accompanied by malaise, anorexia, myalgia, headache, nausea, vomiting, weight loss, erythema and tenderness at the injection site, partial alopecia (reversible), dry mouth, reversible peripheral sensory neuropathy, or signs referable to the centra nervous system. Various indicators of myelosuppression (granulocytopenia, thrombocytopenia, and leukopenia) and abnormal liver function tests, both reversible on cessation of therapy, are regularly observed if high-dose...


Despite the positive composite efficacy result with combination abciximab, there was no mortality benefit (6.6 vs 6.0 for TNK-tPA heparin control). Moreover, significant adverse interactions of treatment with age (RR 1.30 for > 75 yr vs 0.74 for 75, p 0.001) and diabetes (RR 1.35 with vs 0.74 without diabetes, p 0.0007) were observed for the efficacy plus safety end point (Fig. 8). More major bleeding complications, transfusions, and thrombocytopenia occurred in the abciximab group (all p < 0.001), and the rates were three times higher in those older than 75 yr.


Administration of trimethadione (Tridione) may result in hematologic changes, such as pancytopenia (decrease in all the cellular components of the blood), leukopenia, aplastic anemia, and thrombocytopenia. Also reported are various types of skin rashes, diplopia (double vision), vomiting, changes in blood pressure, CNS depression, photosensitivity, and fatal nephrosis. Because these drugs have been associated with serious adverse reactions and fetal malformations, they should be used only when other less toxic drugs are not effective in controlling seizures. The oxazolidine-diones may precipitate a tonic-clonic seizure.


Various auto-antibodies may contribute to tissue injury. Attempts to correlate specific clinical patterns of disease with specific types of auto-antibodies have been partially successful. For example, anti-DNA antibodies have been found in renal glomerular lesions. Sicca syndrome with SLE has been associated with La (SS-B) antibodies. Ro (SS-A) antibodies have been associated with neonatal lupus, congenital complete heart block, and subacute cutaneous lupus. The lupus anticoagulant and anti-cardiolipin antibodies are associated with thrombosis, thrombocytopenia, and increased fetal wastage. Although the titer of ANAs does not necessarily correlate with disease activity, the levels of anti-DNA antibodies may vary with clinical disease. Because results vary, this test cannot be used as the sole guide to therapy. B. Skin. Facial erythema is more common than the classic butterfly eruption as an acute cutaneous manifestation photosensitivity dermatitis and bullous lesions may also...

Sicca syndrome

Much interest has been generated by the finding of auto-antibodies and immune complexes in patients with HIV. Antinuclear antibodies, rheumatoid factor, anti-platelet antibodies, and direct anti-globulin (Coombs') antibodies are examples. A few have clinical significance, including those associated with the development of anemia and thrombocytopenia. Anti-phospholipid antibodies occur in 85 of HIV-infected persons however, they do not appear to be associated with as high a frequency of thrombotic events as in non-HIV-infected patients with the anti-phospholipid syndrome.


During the acute intoxication period, tests for blood alcohol level, serum electrolytes glucose, aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyltransferase (GGT), hematocrit, and amylase can be useful. For the chronic alcoholic, additional laboratory values that should be monitored include albumin, red blood cell indices, white blood cell count, platelet count, prothrombin time, hepatitis B and C screening, vitamin B12, and folate.


Approximately 20 to 30 of patients treated with IFN or PEGIFN and RBV develop adverse events sufficient to warrant dose reduction in one or both of these agents 10-12 . The major reasons to dose reduce PEGIFN include severe flu-like symptoms, neutropenia, thrombocytopenia, thyroid disorders, and psychiatric manifestations (eg, irritability and depression). The major reasons to dose reduce RBV include anemia, nausea, and rash. Aggressive management of these side effects has the potential to limit the number of patients who dose reduce or prematurely discontinue therapy

Storage diseases

The principal treatment is enzyme replacement therapy with macrophage-targeted glucocerebrosidase purified from human placental tissue. Other options include splenectomy for thrombocytopenia and total hip arthroplasty for osteonecrosis. The possible efficacy of bone marrow transplantation and organ transplantation for end-stage disease involving the failure of a single organ is presently being explored.


Ehrlichia chaffeensis is introduced into the skin when the tick takes a blood meal and spreads systemically, infecting monocytes and macrophages in the blood and tissues. The pathologic lesions include perivascular infiltration of lymphocytes and macrophages, some of which are infected with E. chaffeensis, hepatocellular apoptosis, granulomas, and diffuse alveolar damage in the lungs 47 . Perivascular inflammation in the central nervous system is the basis for the meningoencephalitis. Bone marrow biopsies, presumably obtained to evaluate leucopenia, thrombocytopenia, and or anemia, reveal hyperplasia and megakarocytosis (appropriate compensatory responses), erythrophagocytosis, and granulomas 12 . The presence of erythrophagocytosis suggests that peripheral sequestration and destruction of leukocytes, platelets, and red blood cells may be the mechanism of the cytopenias. The granulomas likely play a role in the immune clearance of ehrlichiae, as they are also observed in the murine E....

Donor Selection

Refractory thrombocytopenia aNonalloimmunization causes of refractory thrombocytopenia include drugs, hepatic veno-occlusive disease, hypersplenism, or sepsis. Another more unusual cause of refractory thrombocytopenia is a syndrome resembling thrombotic thrombocytopenic purpura, often associated with the use of cyclosporine, total body irradiation, or the development of acute GVHD.


Risks of Ommaya catheter placement include hemorrhage, poor positioning and the sequelae of intraparenchymal chemotherapy toxicity, malfunction and infection.9 The rate of intraventricular hemorrhage in published series is between 1 to 2.8 .2'4'5'6 Hemorrhages in the cancer population may be related to hematologic abnormalities, such as thrombocytopenia or disseminated intravascular coagulopathy related to the primary cancer or treatment related effects. These risks may be long-standing and occur up to a month after placement, making the coordination of chemotherapy regimens and their expected platelet or white blood cell count nadirs to avoid surgery of utmost importance. For minor abnormalities that are correctable, such as thrombocytopenia, the persistent need for transfusion to keep platelets elevated is a relative contraindication as is need for full anticoagulation.

Ardeparin Normiflo

Hematoma at injection sites is the most common adverse effect. Hemorrhage, although much less frequent than with unfractionated heparin, is still a concern. Hematomas at the site of epidural or spinal anesthesias may result in potentially devastating neurologic compromise, including permanent paralysis. Allergic reactions and skin necrosis are rare. Thrombocytopenia is much less common than with unfractionated heparin. Monitoring of PT or PTT is not necessary. Use in patients with underlying thrombocytopenia or another potential bleeding diathesis should be monitored especially closely. Use in the setting of epidural or spinal anesthesia must be carefully considered. Ardeparin is contraindicated in patients with active hemorrhaging or in those with allergies to porcine products. It should not be administered IM. Hematoma at injection sites is the most common adverse effect. Hemorrhage, although much less frequent than with unfractionated heparin, is still a concern. Hematomas at the...


Randomized controlled trials to evaluate the efficacy of M-CSF as adjunctive therapy for invasive fungal infections (47). M-CSF administration is well tolerated. The major side effects are a transient dose-related thrombocytopenia that may be caused by enhanced function of splenic phagocytic cells (45).


Postoperative morbidity has been reported in eight series (23,24,26,29,30, 33,34,36). An overall assessment can be appreciated from series including patients with CRS and HIPEC 11 grade 2-3 toxicity (26), 16.5 postoperative morbidity (30), and 28.3 major complication rate (33). Including our experience, we can examine the complication rates for 184 patients (Table 3) (23,24,26,29,33,36). Hematologic morbidity was rare. Excluding disseminated intravascular coagulation causing death in one patient, grade 3 leukopenia occurred in 6 184 (3.3 ) and thrombocytopenia in 4 184 (2.2 ). Significant renal toxicity was reported in 8 (4.3 ) patients.


Hodgkin disease, postsplenectomy state, eosinophilic leukemoid reaction, congenital immune deficiency syndromes, Fanconi anemia, thrombocytopenia with absent radii, Kostmann disease, infectious mononucleosis, familial reticuloendotheliosis Familial eosinophilia Irradiation

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