A case report of acute inferior myocardial infarction in a patient with severe hemophilia A after recombinant factor VIII infusion.

RATIONALE: The extent of protective effects of hemophilia against thrombotic events such as myocardial infarction (MI) and other acute coronary syndromes remains to be determined, as major risk factors for cardiovascular disease exist despite factor VIII (FVIII) deficiency. We present a case report of a 41-year-old male with severe hemophilia A and several cardiovascular risk factors. PATIENT CONCERNS: This morbidly obese patient developed chest pressure, followed by chest pain and difficulty in breathing shortly after receiving on-demand treatment with intravenous recombinant FVIII (rFVIII) (turoctocog alfa) dosed per body weight. DIAGNOSES: An electrocardiogram revealed a diagnosis of inferior ST-segment elevation MI. INTERVENTIONS: The patient underwent an urgent coronary angiography using a radial artery approach. During the next 12 months, he received dual antiplatelet treatment, acetylsalicylic acid 100 mg, and clopidogrel 75 mg daily. His treatment for severe hemophilia A was changed to plasma-derived FVIII replacement therapy. OUTCOMES: During this 12-month period, he experienced several small bleeds in his elbows. CONCLUSIONS: The temporal relationship between rFVIII infusion and onset of the MI suggests a possible association; however, apart from obesity, the patient also had other major risk factors for arterial thrombosis, such as hypertension and smoking. Furthermore, atherosclerotic disease and underlying atherosclerotic changes could not be excluded with certainty. This case highlights the importance of studies assessing the impact of excess body weight on rFVIII dosing.

Elevated fibrinogen levels are associated with risk of pulmonary embolism, but not with deep venous thrombosis.

RATIONALE: It is unclear whether elevated plasma fibrinogen is associated with both deep venous thrombosis (DVT) and its complication, pulmonary embolism (PE), and whether elevated fibrinogen is a direct cause of these disorders. OBJECTIVES: We tested the hypotheses that elevated plasma fibrinogen is associated with increased risk of DVT alone, with any PE, and with PE in combination with DVT. METHODS: We studied 77,608 individuals from the Danish general population, of whom 1,679 were diagnosed with DVT alone, 1,119 with any PE, and 272 with both PE and DVT. To test a potential causal relationship using a Mendelian randomization approach, we genotyped for FGB (rs1800790; rs4220) encoding fibrinogen ß chain. MEASUREMENTS AND MAIN RESULTS: Increasing plasma fibrinogen quintiles were associated with increased risk of PE in combination with DVT (P-trend < 0.0001): multivariable adjusted odds ratio was 2.1 (95% confidence interval [CI], 1.2-3.8) in individuals with fibrinogen levels greater than or equal to 4.6 g/L (fifth quintile) versus less than or equal to 3.0 g/L (first quintile). Corresponding odds ratios were 1.7 (95% CI, 1.3-2.3) for any PE (P-trend < 0.0001) and 1.9 (95% CI, 1.0-3.6) for PE in those with DVT (P-trend = 0.003). There was, however, no association after multivariable adjustment between plasma fibrinogen quintiles and risk of DVT alone (P-trend = 0.4). Fibrinogen-increasing alleles were associated with a 7% lifelong increase in plasma fibrinogen levels; however, these genetic variants were not associated with risk of PE or DVT. CONCLUSIONS: Elevated plasma fibrinogen levels are associated with increased risk of PE in combination with DVT but not with DVT alone. Elevated fibrinogen levels per se may not be causally associated with PE or DVT. Limitations include imprecise definitions of PE and DVT.

Vena porta thrombosis in patient with inherited factor VII deficiency.

Most clotting factor VII (FVII)-deficient patients suffer from bleeding episodes and occasionally thromboembolic complications after surgical interventions or replacement therapy. However, thromboses without apparent triggering factors may occur as well. We report a case of a pregnant woman with inherited FVII deficiency and chronic vena porta thrombosis. She presented at 32 weeks of gestation with spontaneously increased international normalized ratio, severe thrombocytopenia and very few unspecific symptoms. The extensive examination of the patient revealed cavernous transformation of the portal vein with well expressed portosystemic collaterals, heterozygosity for three common polymorphisms in FVII gene, associated with reduction in plasma FVII levels, and no other factors predisposing to thrombosis.

Severely impaired von Willebrand factor-dependent platelet aggregation in patients with a continuous-flow left ventricular assist device (HeartMate II).

OBJECTIVES: This study investigated the influence of the mechanical blood pump HeartMate II (HMII) (Thoratec Corporation, Pleasanton, California) on blood coagulation and platelet function. BACKGROUND: HMII is an implantable left ventricular assist device used for the treatment of heart failure. Patients treated with HMII have increased bleeding tendencies. METHODS: We measured agonist-induced platelet aggregation in 16 patients on HMII support. RESULTS: The von Willebrand factor (vWF)-dependent ristocetin-induced platelet aggregation was impaired in 11 of the 16 patients, of which 12 had experienced at least 1 minor or major bleeding episode. The impaired ristocetin-induced platelet aggregation was associated both with decreased specific activity of plasma vWF, presumably due to lack of high molecular weight vWF multimers, as well as with attenuated function of the platelets themselves. CONCLUSIONS: The results imply that HMII treatment is associated with impaired platelet aggregation, which may contribute to an increased tendency to bleed.