Experiences in a family with the Upshaw-Schulman syndrome over a 44-year period.

A family with a novel c.717_del frameshift and a c.3655C > T missense mutation of a disintegrin and metalloproteinase with thrombospondin type I motif, member 13 protein (ADAMTS13) is described. Family members have been under observation for 44 years. Two double heterozygotes have severe early-onset Upshaw-Schulman syndrome and require prophylactic plasma infusions. Analysis reveals that 2 weekly plasma infusions are not sufficient in preventing laboratory evidence of a thrombotic thrombocytopenic purpura (TTP) attack. Both the double heterozygotes also have a heterozygous factor V Leiden G1291A mutation. One underwent splenectomy, which did not reduce the frequency of TTP episodes but resulted in a recurrent pulmonary embolism and has necessitated lifelong anticoagulant therapy. The other has mild chronic renal failure and has had episodes of atrial fibrillation and cerebral infarction. Of the 3 heterozygotes in the family, 1 has had episodes of mild thrombocytopenia.

Activation of coagulation in amniotic fluid during normal human pregnancy.

INTRODUCTION: Amniotic fluid (AF) is an important medium for fetal development which exhibits high procoagulant activities; however, the role of these procoagulants during pregnancy has not been elucidated and might be associated with pregnancy complications. The current study aimed to evaluate factor X (FX) activation and its association with tissue factor (TF), tissue factor pathway inhibitor (TFPI) and coagulation activation markers in AF during normal human pregnancy. METHODS: Activation of FX and concentration of TF, free TFPI, D-dimer and prothrombin fragments (F1+2) were evaluated in AF samples obtained for chromosome analysis from 91 women with normal pregnancy: 65 samples were taken from patients at 16-20 weeks of gestation, 9 samples were drawn at 21-30 weeks and 17 samples--after 30 weeks of gestation. RESULTS: Activation of FX in AF significantly increased during normal pregnancy (from 65±41 to 205±80 equivalent RVV ng/mg total protein, P<0.0001). TF and TFPI levels in AF also rose with gestational age. In contrast, the AF concentration of D-dimer and F1+2, markers of coagulation activation significantly decreased when expressed per mg total protein. Levels of free TFPI correlated with TF (r=0.5, P<0.001), and were 8-fold higher than those of TF during pregnancy. CONCLUSION: High levels of TFPI might be associated with the inhibition of procoagulant activity in amniotic fluid during normal pregnancy, which may account for the rarity of clinical amniotic fluid embolism.