Juan Chediak

von Willebrand's disease and pregnancy: Management during delivery and outcome of offspring

Six patients having different subtypes of von Willebrands disease were followed up during eight complete pregnancies. Two additional pregnancies terminated in spontaneous abortions. Five pregnancies ended in cesarean section either because of obstetric problems (three) or electively (two) to avoid infant bleeding. Three deliveries were complicated by vaginal bleeding attributed to von Willebrands disease, while bleeding during two deliveries had clear obstetric causes. Only two deliveries were associated with no bleeding complications. Five newborn babies were found to have von Willebrands disease. One of them was born with a head hematoma. Management, which included cryoprecipitate and desmopressin (Stimate), is discussed. It is important to manage each case individually since obstetric parameters and severity of bleeding disorder must be known before treatment is planned.

Cycles of Agglutination-Disagglutination Induced by Ristocetin in Thrombasthenic Platelets

Summary. An oscillatory pattern of platelet agglutination‐disagglutination in response to Ristocetin (R) at narrow concentration ranges was observed in citrated platelet rich plasma (PRP) of 10 patients with Glanzmanns thrombasthenia. The cyclic pattern decreased in intensity over time, was reproducible, and was not pH dependent. Formalin‐fixed thrombasthenic platelets agglutinated with R but did not show a cyclic pattern.

Studies on a circulating anticoagulant inhibiting factor XI in a patient with congenital deficiency and carcinoma of the prostate

An inhibitor of plasma thromboplastin antecedent (PTA, factor XI), measured in coagulant and radioimmunoassays, was detected in a 60‐year‐old man with carcinoma of the prostate who had no evidence of a bleeding tendency. Family studies indicated that the patient was either a homozygote or a heterozygote for hereditary factor XI deficiency. In contrast to earlier described patients with factor XI deficiency in whom inhibitors were detected, the patient was unaware of having been transfused with blood or blood products at any time before the discovery of the inhibitor. The inhibitor of factor XI in the patients plasma appeared to be predominantly in the IgG4 fraction and to be directed at a locus on the factor XI molecule other than the active site; it did not block the amidolytic properties of activated factor XI (XIa). Rather, it appeared to block adsorption of factor XI to negatively charged surfaces. The inhibitor interfered with measurement of other components of the intrinsic pathway of thrombin formation, perhaps explaining the low titres of other coagulation factors of the intrinsic system reported in patients with strong inhibitors directed against factor XL.

ABSENCE OF RISTOCETIN AGGREGATION FACTOR FROM THE SKIN OF A PATIENT WITH VON WILLEBRAND'S DISEASE

Samples of apparently normal skin from one patient with von Willebrands disease (vWD) and five patients without vWD were examined with fluorescein-tagged antiserum to the component of factor VIII required for aggregation of platelets by ristocetin (VIII-R.A.F.). No evidence of VIII-R.A.F. was found in the vWD skin, while bright granules were seen on and/or in the endothelial cells of dermal capillaries in all patients without vWD. VIII-R.A.F. granules were also found in the interstitial vasculature of all of twelve renal-biopsy specimens from patients without vWD. These observations support the concept that an abnormality of the vascular endothelium is involved in the pathogenesis of vWD.

Quantitative and qualitative platelet abnormalities during pregnancy

In a 1-year period, 15 of 4048 pregnant women were found to have thrombocytopenia during their first prenatal visit. Their qualitative and quantitative platelet abnormalities were followed up prospectively for 1 to 6 months post partum. Platelet counts returned to normal in 14 of 15 patients 4 to 6 weeks post partum, von Willebrand factor antigen and ristocetin cofactor activity were low in three of 15 patients 4 to 6 weeks post partum, but had been normal during the antepartum period. Two of these three patients had prolonged bleeding times ante partum and post partum. All three patients subsequently were found to have mild type I von Willebrand disease. Six patients had detectable platelet antibodies. Neonatal thrombocytopenia was found in one term infant of a patient with mild thrombocytopenia and negative platelet antibodies. This study suggests that mild, transient, isolated thrombocytopenia can occur in an otherwise normal pregnancy and its incidence may be lower than previously reported. Extensive testing is not indicated unless there is an associated prolonged bleeding time. The possibility of von Willebrand disease or a qualitative platelet disorder should be considered.

Pulmonary function in hemophiliac patients treated with commercial factor VIII concentrates

Pulmonary function was tested before and after the administration of a commercial preparation of factor VIII concentrate in 20 patients with hemophilia A. The material was infused through the filter provided by the manufacturer, which is supposed to remove particles larger than 170 mu. Baseline information showed that patients who smoke had a lower pulmonary diffusing capacity for carbon monoxide than nonsmokers (22.9 +/- 4.2 ml/minute/mm Hg, p less than 0.01). The administration of factor VIII was not associated with clinical abnormalities. There was a small reduction in carbon monoxide diffusing capacity (27 +/- 5.8 to 26.2 +/- 5.9 ml/minute/mm Hg, p = 0.03), which was no longer significant after carbon monoxide diffusing capacity was corrected for lung volume (5.66 +/- 1.32 to 5.54 +/- 1.34, p greater than 0.06). This study does not support the need for 40 mu filtration of factor VIII concentrate.

Correction of clot retraction in thrombasthenia by ATP and ristocetin

Abstract The effect of ATP and ristocetin on clot retraction was examined in patients with Glanzmanns thrombasthenia. ATP alone, or ristocetin alone, when added to freshly drawn whole blood from thrombasthenic patients, produced some correction of clot retraction. However, combining these two agents completely normalized clot retraction. These results indicated that ATP and ristocetin act synergistically in restoring the ability of the thrombasthenic platelets to produce clot retraction.