De novo mutation of the platelet glycoprotein Ib alpha gene in a patient with pseudo-von Willebrand disease.

Pseudo (or platelet-type)- von Willebrand disease (vWD) is a very rare autosomal dominant bleeding disorder caused by an abnormal hyper-responsiveness of the platelet membrane glycoprotein (GP) Ib/IX complex, the receptor for von Willebrand factor. We found a heterozygous missense mutation in the GPIb alpha gene in a sporadic case with pseudo-vWD: Met (ATG) to Val (GTG) at residue 239. The mutation was not detected in either parent. Investigation of three variable number of tandem repeat loci, D1S80 (MCT118), vWA and D17S5 (YNZ22), confirmed paternity and the de novo origin of the mutation. Furthermore, we have shown by the TaqI polymorphism analysis, which is located downstream of the GPIb alpha gene, that the mutation occurred in the maternal allele. This is the first description of de novo mutation occurred in pseudo-vWD and/or platelet GPIb alpha gene.

The use of low dose Orgaran in heparin-induced thrombocytopenia associated with in vitro platelet aggregation at higher Orgaran concentrations.

We report a case of heparin-induced thrombocytopenia with in vitro antibody cross-reactivity by platelet aggregometry to both low molecular weight heparin and the heparinoid Org 10172 (Orgaran). The in vitro reactivity with Orgaran was only present at the upper limit of concentrations that would normally be used therapeutically. Low dose Orgaran therapy was initiated, allowing successful renal replacement therapy without invoking further thrombocytopenia or thrombosis. Interestingly, in vitro platelet aggregometry following treatment did not reveal increasing sensitivity to Orgaran. This case indicates that negative in vitro platelet aggregometry at defined lower concentrations of Orgaran may predict in vivo safety at the same levels despite positive platelet aggregometry reactions at higher concentrations of Orgaran.

Acquired heparin-like anticoagulants: a second case in metastatic breast carcinoma and literature review.

We report the second case of an acquired heparin-like anticoagulant in a patient with disseminated breast carcinoma. All but one of the small numbers of other cases have also been associated with an underlying malignancy. We comment on the distinction between an immunoglobulin and proteoglycan causing the antithrombin effect and suggest points of interest for consideration in any future cases together with a review of treatment options.

Quinine-induced disseminated intravascular coagulation.

Recurrent disseminated intravascular coagulation occurred in 3 women after ingestion of quinine tablets for cramp. All had circulating quinine-dependent antibodies to platelets and in 2 there was initial evidence of antibody consumption, with low titres that rose steeply over the next few days and remained high for many months.

Assessment of D dimer assays for the diagnosis of deep vein thrombosis.

Sixty-two patients with suspected deep vein thrombosis were subjected to venography and to plasma D dimer assay by both rapid latex agglutination and enzyme immunoassay methods. The latex agglutination method was insensitive to the presence of deep vein thrombosis. In contrast, the enzyme immunoassay method was sensitive although of low specificity and for technical reasons not suitable for performance as an emergency test.

Influence of spinal and general anaesthesia on haemostasis during total hip arthroplasty.

One hundred and one patients with osteoarthritis were randomly allocated to undergo total hip arthroplasty under either spinal (subarachnoid) or general anaesthesia. Venous blood was sampled before, during and after surgery and on the 5th day after operation to study the haemostatic mechanism. There were no preoperative differences between the two anaesthetic groups. Although there was pronounced individual variability, similar patterns of change in coagulation, platelets and fibrinolysis were seen in both groups. However, there were significant differences between the two groups in platelet count, thrombin production, and Factor VIIIRAg in the intra- and immediate postoperative periods. Also, compared with general anaesthesia, there was less intraoperative activation of fibrinolysis, as measured by the euglobulin clot lysis time, with spinal anaesthesia. These differences suggest slight modification of the haemostatic response to surgery with spinal anaesthesia, which could be consistent with a neuroendocrine mechanism. By the 5th day both groups exhibited a very similar "hypercoagulable" postoperative state.

Twin pregnancy and parturition in a patient with the Bernard Soulier syndrome.

A patient with the Bernard Soulier Syndrome was successfully delivered of twins. The pregnancy was complicated by slight bleeding from the uterus during the first 8 weeks, by cord prolapse necessitating emergency caesarean section, and by moderate post partum haemorrhage. The management of pregnancy in the Bernard Soulier Syndrome is discussed.

A functional assay of protein C in human plasma.

A functional assay for protein C in plasma is described in which barium eluates of plasma are incubated with bovine thrombin and rabbit thrombomodulin to activate protein C. The activated protein C solution is added to an activated partial thromboplastin time (APTT) system containing normal plasma and an APTT reagent (Dade ActinR). The prolongation of coagulation time after recalcification in this system is taken as a measure of the anticoagulant activity of protein C. When expressed as per cent of the value in pooled normal plasma, the results obtained by this method in 34 normal controls and in 3 untreated patients with protein C deficiency were very similar to those obtained by radioimmunoassay of protein C. In 2 patients with protein C deficiency and 23 patients without, all on dicoumarol or warfarin treatment, the anticoagulant activity of protein C was less than its antigen concentration. The day to day analytical coefficient of variation (SD/mean) was 12% at the 100% level (n = 12), and 10% at the 25% level (n = 12).

Haemostasis in heat stroke.

A patient with moderately severe heat stroke was studied with particular attention to changes in haemostasis. Activation of fibrinolysis, a probable failure of hepatic synthesis of coagulation factors and severe thrombocytopenia were observed, but there was no definite evidence for disseminated intravascular coagulation (DIC). It is suggested, however, that in heat stroke of greater severity the more extensive tissue breakdown may lead to DIC. If DIC is superimposed on the above changes in haemostasis it is likely to be both sudden and overwhelming.