Acquired haemophilia in association with organ-specific autoimmune disease.

A 72-year-old woman presented with multiple sites of soft tissue bleeding and a left ulnar neuropathy due to a compartment syndrome. There were also clinical signs of hypothyroidism. Factor VIII:C (FVIII) levels were 6% and a FVIII inhibitor with a titre of 9 Bethesda units was detected. She had biochemical evidence of hypothyroidism and high titres of antithyroid antibodies were detected. Two episodes of life- or limb-threatening haemorrhage were successfully treated with FEIBA. The inhibitor disappeared following 2 months of immunosuppression with oral cyclophosphamide and corticosteroids. She then developed autoimmune haemolytic anaemia, which responded to further immunosuppression with oral prednisolone. The association between acquired haemophilia and systemic autoimmune disorders such as systemic lupus erythematosis is well recognized, but our description of an association with organ-specific autoimmunity is more unusual.

Combined risk factors contributing to cerebral venous thrombosis in a young woman.

Cerebral venous thrombosis is a rare condition affecting predominantly adolescents or young adults. The presentation is often non-specific, and delay in diagnosis is common. The otolaryngologist may be consulted about the radiological findings of lateral sinus thrombosis and mastoid changes. The association of congenital thrombophilia with unusual presentations of venous thrombosis, especially in young individuals is now well documented. We present a case of lateral and sagittal sinus thrombosis complicated by cerebral venous infarction in a girl with protein C deficiency and masked mastoiditis. Unusual forms of venous thrombosis, including cerebral venous thrombosis may develop in association with a single risk factor for thrombosis, but additional risk factors should be sought especially when thrombosis presents in very young individuals. This case draws attention to the multi-causal nature of cerebral venous thrombosis in young adults, and highlights the issue of masked mastoiditis. A coordinated approach by otolaryngological and haematological teams is recommended in such cases.

In vivo platelet activation in atherothrombotic stroke is not determined by polymorphisms of human platelet glycoprotein IIIa or Ib.

Platelet membrane glycoprotein polymorphisms are candidate risk factors for thrombosis, but epidemiological data are conflicting. Thus, demonstration of a genotype-dependent alteration in function is desirable to resolve these inconsistencies. We investigated in vivo platelet activation in acute thrombosis and related this to platelet genotype. Frequencies of the 1b and 2b alleles of the HPA 1a/1b and HPA 2a/2b platelet glycoprotein polymorphisms were determined in 150 (52 men/98 women, mean age 58.3 years) patients with atherothrombotic stroke, and the influence of genotype on markers of platelet activation was assessed. Platelet P-selectin (CD62P) expression and fibrinogen binding was measured using whole blood flow cytometry within 24 h of stroke and 3 months later in 77 patients who provided a repeat blood sample. Results were compared with matched controls. Neither the 1b allele [allele frequency 0.11 vs. 0.13, odds ratio (OR) confidence interval (CI) 0.8 (0.5-1.3)] nor the 2b allele [0.09 vs. 0.07, OR (CI) 1.4 (0.8-2.4)] was significantly over-represented in patients. Increased numbers of activated platelets were found following stroke (acute mean P-selectin expression 0.64% vs. control 0.35%, P < 0.001; acute mean fibrinogen binding 1.6% vs. control 0.9%, P < 0.001). Activation persisted in the convalescent phase (P < 0.001 and P = 0.005 vs. controls for P-selectin and fibrinogen respectively). Expression of P-selectin and fibrinogen was not influenced by either the HPA 1a/1b genotype (P > 0.95 for each marker, Scheffe's test) or the 2a/2b genotype (P > 0.95 for each). Although persisting platelet activation is seen in atherothrombotic stroke, it is independent of HPA 1a/1b and 2a/2b genotypes. These data suggest an underlying prothrombotic state, but do not support the polymorphisms studied as risk factors for thrombotic stroke in this population.

Plasma homocysteine concentrations in the acute and convalescent periods of atherothrombotic stroke.

BACKGROUND AND PURPOSE: Homocysteine is a proposed causal risk factor for atherosclerosis, but this remains controversial. We measured fasting plasma homocysteine concentrations immediately after atherothrombotic stroke and in the convalescent period to investigate this controversy. METHODS: One hundred six patients (59 men and 47 women, mean age 57.2 [25 to 70] and 56.5 [26 to 69] years, respectively) were recruited within 24 hours of admission, and 82 patients were resampled at least 3 months later. Fasting total plasma homocysteine (tHcy) concentrations were measured by high-performance liquid chromatography. RESULTS: Median tHcy in the acute phase of stroke was not significantly higher than in matched control subjects (men 9.2 [range 4.4 to 22.8] versus 8.7 [4.9 to 20] micromol/L, P:=0.09, Mann-Whitney U: test; women 8.1 [4.8 to 32.3] versus 7.6 [3.3 to 14.4] micromol/L, P:=0.58). Median plasma concentrations increased significantly in the convalescent period (from 8.5 [4.8 to 19.2] to 10.1 [4.3 to 31.5] micromol/L, P:<0.001, Wilcoxon signed rank test) and were then significantly higher than in control subjects in both men and women (P:=0.03 and 0.05, respectively, Mann-Whitney U: test). This did not appear to be explained by alteration in the known covariates red-cell folate, serum B(12), or creatinine concentrations. CONCLUSIONS: Homocysteine concentrations are not elevated after recent atherothrombotic stroke but rise in the convalescent period. These data do not support the hypothesis that raised plasma homocysteine concentrations predate atherothrombotic stroke. Instead, they offer an explanation for the discrepancies between prospective and retrospective studies and suggest that elevated tHcy levels may be caused by the disease process itself.

Platelet glycoprotein IIIa polymorphism HPA 1b (PlA2): no association with platelet fibrinogen binding.

The role of the platelet glycoprotein (GP) IIIa polymorphism HPA 1b (PlA2) in the risk of arterial thrombosis is controversial. We investigated the effect of the 1b allele on platelet fibrinogen binding by flow cytometry. Samples from 35 healthy platelet and plasma donors possessing the 1b allele were compared with 35 1a/1a donors. We found no allele-dependent difference in percentage of platelets binding fibrinogen (P = 0.6), nor in mean cell fluorescence (P = 0.3) following stimulation with ADP. These results render it unlikely that any relationship between the 1b polymorphism and arterial thrombosis is mediated by a significant effect on fibrinogen binding.

Sea-blue histiocytosis and pancytopaenia associated with chronic total parenteral nutrition administration.

A 22-year-old female on chronic total parenteral nutrition for short bowel syndrome presented for investigation of pancytopaenia and hepatosplenomegaly. Bone marrow examination revealed an infiltrate of sea-blue histiocytes and cytochemistry confirmed these to be lipid laden macrophages. The total amount of fat in the feeding regimen was subsequently reduced, and there has been a partial haematological improvement. The occurrence of sea-blue histiocyte syndrome complicating the fat emulsion component of chronic total parenteral nutrition has been reported recently. To our knowledge this report is the first where reduction in the lipid content of the feeding regimem has resulted in an improvement in the degree of pancytopaenia.