ristocetin and Uterine-Hemorrhage

von Willebrand disease is caused by either a quantitative or qualitative defect in von Willebrand factor (VWF). Patients may have extensive mucosal bleeding (because of platelet dysfunction) and prolonged bleeding after surgery (because of factor VIII deficiency). Up to 6 different subtypes of the disease have been described, and diagnosis is based on clinical suspicion and laboratory confirmation. Accurate diagnosis is of paramount importance because therapy will vary according to the subtype. Bleeding complications during pregnancy are more frequent when levels of the von Willebrand ristocetin cofactor assay and factor VIII levels are <50 IU/dL. In such cases, therapy before any invasive procedure or delivery must be instituted. The mainstays of therapy are desmopressin and plasma concentrates that contain von Willebrand factor. Delayed postpartum hemorrhage may occur, despite adequate prophylaxis. Frequent monitoring and continued prophylaxis and/or treatment are recommended for at least 2 weeks after delivery.

Topics: Blood Component Transfusion; Chromosomes, Human, Pair 12; Continuity of Patient Care; Deamino Arginine Vasopressin; Delivery, Obstetric; Factor VIII; Female; Hemostatics; Humans; Mutation; Postpartum Hemorrhage; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Ristocetin; Uterine Hemorrhage; von Willebrand Diseases; von Willebrand Factor

Spontaneous EDTA-independent cold platelet agglutination is a rare phenomenon that produces pseudothrombocytopenia when blood samples are analyzed in automated cell counters. We report a case of platelet cold agglutinins and an analysis by flow cytometry. A 49 year old woman presented with abnormal vaginal bleed secondary to uterine fibroids. Platelet clumping was observed in blood samples taken in EDTA-, heparin- and citrate-containing tubes. In flow cytometric tests, patient serum agglutinated 16% of normal platelets at 22 degrees C, and 7% of platelets after incubation at 37 degrees C; in contrast, 3% and < 1% of platelets were agglutinated at 22 and 37 degrees C, respectively, after incubation with normal serum. Minimal agglutination (< 10%) was observed with patient serum at a titre of 1:5 or at temperatures > 30 degrees C. After incubation at 4 degrees C, IgM antibody and C3 were increased on the patient's platelets; no significant amount of IgM or C3 was detected on normal platelets. The specificity of the platelet cold agglutinin was determined by competitive inhibition by monoclonal anti-CD41(GPIIbIIIa). Before the addition of monoclonal antibody, patient's serum agglutinated 16% of normal platelets at 22 degrees C; after addition of anti-CD41 only 2% of the platelets were agglutinated. This blocking effect was not observed with anti-CD42. The patient's platelets functioned normally as determined by CD62 and CD63 expression in response to thrombin, normal platelet aggregation in response to collagen, ADP, and ristocetin, and a normal template bleeding time. In summary, platelet agglutination by a platelet cold agglutinin was quantitated by flow cytometry, the responsible antibody was characterized as a low titre IgM with minimal activity > 30 degrees C, and competitive binding studies supported the GPIIbIIIa complex as the binding site for the antibody. Since the antibody did not affect platelet function, we believe that these patients will not suffer complications from their platelet cold agglutinin, but it could pose a problem under circumstances such as cardiac surgery with hypothermia.

Topics: Adenosine Diphosphate; Agglutinins; Antibody Specificity; Antigens, Human Platelet; Blood Platelets; Cold Temperature; Collagen; Cryoglobulins; Edetic Acid; False Positive Reactions; Female; Flow Cytometry; Humans; Immunoglobulin M; Leiomyomatosis; Middle Aged; Platelet Aggregation; Platelet Function Tests; Platelet Glycoprotein GPIIb-IIIa Complex; Ristocetin; Thrombocytopenia; Uterine Hemorrhage; Uterine Neoplasms