Cirrhosis thrombocytopenia

Crixivan 400-mg caps IDV 800 mg + RTV 100 bid IDV 800 mg + RTV 200 mg bid insufficiency due to cirrhosis 600 mg q8hours Take 1 hour before or 2 hours after heavy meals, or concomitantly with low-fat meal No restrictions when used with RTV nausea indirect hyperbilirubinemia hyperlipidemia headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, alopecia, hemolytic anemia hyperglycemia fat maldistribution increased bleeding episodes in patients with hemophilia (less than RTV)... 

Toxicities are GI (stomatitis, diarrhea, nausea, vomiting), hematologic (thrombocytopenia, leukopenia), pulmonary (fibrosis, pneumonitis), and hepatic (elevated enzymes, rare cirrhosis). Concomitant folic acid may reduce some adverse effects without loss of efficacy. Liver injury tests (aspartate aminotransferase or alanine aminotransferase) should be monitored periodically, but a liver biopsy is recommended during therapy only in patients with persistently elevated hepatic enzymes. MTX is teratogenic, and patients should use contraception and discontinue the drug if conception is planned. 

Complex coagulation derangements can occur in cirrhosis. These derangements include the reduction in the synthesis of coagulation factors, excessive fibrinolysis, disseminated intravascular coagulation, thrombocytopenia, and platelet dysfunction. 

An elevation of prothrombin time was the single most reliable manifestation of cirrhosis. The combination of thrombocytopenia, encephalopathy, and ascites had the highest predictive value. 

A 42-year-old woman, treated with octreotide infusion 50 mg/hour for cirrhosis-related gastrointestinal bleeding on two occasions 9 months apart, had an immediate fall in platelet count on both occasions, resolving after octreotide withdrawal (26). The thrombocytopenia was not severe (nadir platelet counts 62 and 55 x 109/1) and did not require specific treatment. 

Thrombopoietin, a 65-85 kDa glycosylated protein, is constitutively expressed by a variety of organs and cell types. Hepatocytes appear to be the major source of human thrombopoietin, and patients with cirrhosis and thrombocytopenia have low serum thrombopoietin levels. Recombinant thrombopoietin is produced by expression in human cells the recombinant product contains two intramolecular disulfide bonds and a number of carbohydrate side chains. 

Typical side effects are constitutional in nature, including a flu-like syndrome within 6 hours after dosing in more than 30% of patients that tends to resolve upon continued administration. Other potential adverse effects include thrombocytopenia, granulocytopenia, elevation in serum aminotransferase levels, induction of autoantibodies, nausea, fatigue, headache, arthralgias, rash, alopecia, anorexia, hypotension, and edema. Severe neuropsychiatric side effects may occur. Absolute contraindications to therapy are psychosis, severe depression, neutropenia, thrombocytopenia, symptomatic heart disease, decompensated cirrhosis, uncontrolled seizures, and a history of organ transplantation (other than liver). Alfa interferons are abortifacient in primates and should not be administered in pregnancy. 

Selinger, S., Tsai, J., Pulini, M., Saperstein, A., Taylor, S. Autoimmune thrombocytopenia and primary biliary cirrhosis with hypoglycemia and insulin receptor autoantibodies. Ann. Intern. Med. 1987 107 686 - 688... 

Although inhibition of stem-cell proliferation is the most likely mechanism of hematological toxicity, increased platelet hepatic uptake has been suggested to account for thrombocytopenia (227). Raised serum thrombopoietin concentrations were found in patients with interferon alfa-induced thrombocytopenia (228). However, there is evidence that serum thrombopoietin concentrations in patients who have had thrombocytopenia during interferon alfa treatment for chronic viral hepatitis C either do not increase (in patients with compensated cirrhosis) or increase only moderately and less than expected (in non-cirrhotic patients) (229). The authors proposed that interferon alfa impairs liver production of thrombopoietin, raising the possibility of testing thrombopoietin administration in patients with severe thrombocytopenia before or during treatment with interferon alfa (230). 

Like all diuretics, the thiazides can cause electrolyte abnormalities, such as hypokalemia and hyponatremia, and dehydration. These complications are uncommon in patients with uncomplicated hypertension, but are more common in patients with heart failure or decompensated hepatic cirrhosis with secondary hyperaldosteronism. Until a patient is accustomed to the effect of a diuretic, dizziness may be experienced. Serum lipid concentrations are slightly raised acutely and hyperglycemia can occur during long-term therapy. Rare effects are thrombocytopenia, rashes, drug fever, cholestatic jaundice, pancreatitis, and precipitation of hepatic... 

Hg, Portal hypertension occurs when there is obstruction to portal flow anywhere along its course. The causes of obstruction leading to portal hypertension are classified by site (1) presinusoidal, (2) sinusoidal, and (3) postsinusoidal. Pre-sinusoidal portal hypertension is most commonly caused by portal vein thrombosis or schistosomiasis but may also occur with increased portal flow, such as occurs with Felty syndrome (a combination of chronic rheumatoid arthritis, splenomegaly, leukopenia, pigmented spots on the lower extremities, and sometimes other evidence of hyper-splenism, such as anemia and thrombocytopenia). Sinusoidal hypertension is most commonly caused by cirrhosis but may occur transiently with acute and chronic hepatitis or acute fatty liver. The most important cause of postsinusoidal hypertension is hepatic vein occlusion or Budd-Chiari syndrome, in which sudden obstruction or occlusion of the... 

Kajihara M, Kato S, Okazaki Y, Kawakami Y, Ishii H, Ikeda Y, et al. A role of auto antibody-mediated platelet destruction in thrombocytopenia in patients with cirrhosis. Hepatology 2003 37 1267-76. 

Aoki Y, Hirai K, Tanikawa K. Mechanism of thrombocytopenia in liver cirrhosis Kinetics of indium- 111 tropeolin-labeled platelets. Eur J Nucl Med 1993 20 123-129. 

Absolute contraindications to use of interferon include current or past psychosis or severe depression, neutropenia or thrombocytopenia, organ transplant (except liver), symptomatic heart disease, decompensated cirrhosis, and uncontrolled seizures. Relative contraindications to interferon include uncontrolled diabetes and autoimmune disorders. 

Because a-interferon therapy can exacerbate autoimmune disorders, it is important to exclude autoimmune diagnoses before initiating therapy. Thrombocytopenia and granulocytopenia are more common in patients with cirrhosis and hypersplenism. The psychiatric complications are especially severe in those with severe liver disease, occur in up to 20% of patients, and are the most common dose-limiting side effects. Therapy should be discontinued if serious complications occur. The dose of a-interferon must be reduced in 10% to 40% of patients. Treatment must be discontinued because of adverse effects in 5% to 10% of patients. For many patients, reassurance that the side effects are therapy related, not severe, and will disappear when therapy is stopped is sufficient. It is always important to reassure both patient and family, especially when psychiatric side effects are evident. These points are critical given that patient adherence is crucial to the ultimate success of HCV treatment. ... 

D-penicillamine is so named because it was first isolated as an amine, from the degradation products of penicillin by Abraham et al [87]. Later studies showed the characteristic chemical behavior of D-penicillamine which involve three types of reactions, formation of disulphide links, formation of thiazolidine rings, and formation of metal complexes and chelates [67]. It was first used in 1956 in the treatment of Wilson s disease [88]. D-penicillamine has since been used in the treatment of many diseases, such as cystinuria [89], rheumatoid arthritis [90-92], systemic sclerosis [93], primary bdiary cirrhosis [94], heavy metal poisoning due to lead [95], cadmium [%], and mercury [97], and hyperviscosity syndrome [99]. In rheumatoid arthritis, D-peni-cdlamine has been widely accepted as an effective second line treatment. Despite of its effectiveness, it causes many adverse effects, such as skin rashes [99,100], taste abnormalities [100,101], hepatic dysfunction [102-104], gastrointestinal toxiciiy [99,105], proteinuria [100,106], hematuria [107, 108], thrombocytopenia [92, 109], aplastic anemia [110], lupus-like syndrome [111, 112], Goodpasture s-tike pulmonary renal syndrome [113-115], vasculitis [116,117], myasthenia gravis [118-122], polymyositis [123, 124], and dermatomyositis [125]. 

Penicillamine is a chelating agent which binds copper, mercury, zinc, and lead. It has been used to treat poisoning from these chemicals and also for disorders of copper metabolism such as Wilson s disease and primary biliary cirrhosis. Penicillamine has been tried in scleroderma and arthritis. Hypersensitivity reactions are common. About 20%-30% of the patients show hypersensitivity reactions suchs as morbilliform exanthema, urticaria, purpura, anorexia, lymphadenopathy, leukopenia, and thrombocytopenia (Meyboom 1975 Balme and Huskisson 1977). More severe skin symptoms associated with penicillamine therapy are Stevens-Johnson syndrome, pemphigus, myasthenia gravis, cholestatic jaundice (Barzilai et al. 1978), nephropathy (Lange 1978) and lupus-like syndrome (Harpey et al. 1972). 

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