Fatal cerebral infarctions in diabetic ketoacidosis in a child with previously unknown heterozygosity for factor V Leiden deficiency.

An 11-year-old boy with poorly controlled diabetes had sudden collapse after the development of lower extremity deep venous thrombosis, with fatal cerebral infarctions. He was heterozygous for factor V Leiden deficiency. This case emphasizes the value of cranial imaging after initial resuscitative treatment of neurologic collapse in diabetic ketoacidosis.

Hypopituitarism, deficiency of factors V and VIII and von Willebrand factor: an uncommon association.

A 9 year-old boy with hypopituitarism and blood coagulation abnormalities is presented and discussed. The association between acquired von Willebrand disease and hypothyroidism has been reported but the combination of hypopituitarism and coagulopathy is unusual. Combined multiple clotting deficiencies are rare and, when present, factors V and VIII is the commonest association. Although it is known that hypothyroid patients may have a decrease in von Willebrand's factor (vWf) and factor VIII, there are no reports of hypopituitarism associated with combined deficiency of factors V, VIII, and vWf.

Rapid detection of factor V Leiden (FVQ506) by non-radioactive single strand conformation polymorphism (SSCP).

The transition G-->A at position 506 of the factor V gene is responsible for resistance to the anticoagulant effect of activated protein C (APC-resistance), and represents the most common hereditary risk factor for venous thrombosis. A comparison of the ability of non-radioactive single-strand conformation polymorphism (SSCP) and of a standard PCR procedure followed by further digestion with MnlI to detect this factor V gene (FVQ 506) transition indicates that these is a good agreement between the two methods. Non-radioactive SSCP analysis therefore represents a rapid and sensitive alternative for the diagnosis of this important point mutation.

[Activated protein C resistance as a cause of thrombophilia]. / Resistencia a la proteína C activada como causa de trombofilia.

The proportion of identifiable causes of familial thrombophilia has increased from 5-10% to 60-70% since the identification of activated protein C resistance (aPCR) in February 1993 by Dahlbäck et al. A mutation in the factor V gene (G-->A, 1691) leads to the so called Leiden mutation (R 506 Q) that produces a mutated factor V resistant to the catalytic action of activated protein C (aPC), yet normal in its procoagulant properties. This recently identified aPCR is in Nordic populations the most prevalent and well defined genetic defect associated with disease so far described. Its prevalence in the general population ranges from 0% to up to 15% and suggests that a positive genetic selection pressure has been involved. The aPCR phenotype can be assessed in vitro by measurement of the prolongation of the activated partial thromboplastin time in the presence of aPC, whereas the aPCR genotype is studied using polymerase chain reaction searching for the Arg to Gln mutation in the coagulation factor V gene. Some acquired conditions such as the presence of lupus anticoagulants, antiphospholipid antibodies, pregnancy, liver disease and contraceptives may lead into the aPCR phenotype. The aPCR search must be the initial step in the study of a patient with thrombophilia, either inherited or acquired aPCR together with protein C, protein S and antithrombin III explain 60 to 70% of cases of familial thrombophilia.

Hereditary combined deficiency of clotting factors V and VIII with involvement of von Willebrand factor.

A family is described in which two brothers, with a significant haemorrhagic disorder, are affected by combined factor V/VIII deficiency. In one of these patients an abnormal decrease of von Willebrand factor was also observed. Family studies suggest that both of the brothers are homozygous for a recessive gene. Normal laboratory results were found in eight other family members although seven of them had reported a mild bleeding tendency. The results indicate that hereditary combined factor V/VIII deficiency is a heterogeneous disorder and that defects of von Willebrand factor might be involved in the aetiology of the disease in some families.