Kathelijne Peerlinck

Mild haemophilia: a disease with many faces and many unexpected pitfalls

Summary.u2002 Despite major advances in diagnosis and treatment, the management of patients with mild haemophilia (MH) remains a major challenge. Mild haemophilia is defined by factor levels between 0.05 and 0.40u2003IUu2003mL−1. The bleeding associated with mild haemophilia is most frequently episodic, occurring during surgery or following trauma. Spontaneous bleeding is rare. Diagnosis is sometimes delayed because of insensitivity of screening clotting assays or discrepancies in factor VIII activity as measured by different assays. The treatment of choice in mild haemophilia A is desmopressin, which typically induces a 2–6‐fold increase of factor VIII over baseline. However, desmopressin has its limitations in this setting such as the occurrence of tachyphylaxis and failure to respond in an undetermined proportion of patients. Factors underlying poor biological response or magnitude of response to desmopressin are incompletely understood. Inhibitor development in mild haemophilia is particularly distressing. This complication arises at an older age in this patient group because of infrequent need for factor VIII replacement. Inhibitors in mild haemophilia patients often cross‐react with endogenous factor VIII resulting in severe spontaneous bleeding frequently in a postoperative setting. Intensive perioperative use of factor VIII and some specific mutations induce a particularly high risk for inhibitor development, but risk factors are incompletely understood. For reasons of the older age of the patients, treatment of bleeding with bypassing agents may cause major thrombotic complications. Data on therapeutic options for inhibitor eradication in patients with mild haemophilia are particularly scarce. With increased life‐expectancy for all haemophilia patients, the group of elderly patients with mild haemophilia requiring major surgery will further increase. Prevention of inhibitors, particularly in this patient group, should be a major topic of interest in both clinic and research.

Drugs affecting blood coagulation, fibrinolysis, and hemostasis

Publisher Summary This chapter discusses several drugs that affect blood coagulation, fibrinolysis, and hemostasis. Co-trimoxazole and coamoxiclav should be avoided in patients taking coumarins. If no therapeutic alternative is available, increased monitoring of INR values is warranted to prevent overanticoagulation and potential bleeding complications. The effects on activated partial thromboplastin time and the incidence and clinical relevance of antihirudin antibodies in patients treated with lepirudin have been studied using data from two prospective multicenter studies, in which patients with heparin-induced thrombocytopenia received one of four intravenous lepirudin dosage regimens. Fatal aplastic anemia has been reported in two patients taking clopidogrel. Aplastic anemia was diagnosed 5 months after starting clopidogrel in the first patient and after 3 months in the second. Both patients died from infection (sepsis and pneumonia). Except for allopufinol in the first case, these patients did not take any medications associated with aplastic anemia Dipyridamole has been marketed since 1959, originally as an antianginal drug on the basis of its acute coronary vasodilatory effect; the addition of atropine to dipyridamole for stress echocardiography increases the sensitivity of the test without loss of specificity and without worsening its safety profile. A lupus-like illness (fever, rash, arthritis, renal involvement, and positive antinuclear and antihistone antibodies) developed in three patients 2-8 weeks after they started to take ticlopidine.