Isolated deficiency of platelet procoagulant activity.

This is a study of a 34 year old woman with a moderate to severe bleeding disorder in whom impaired platelet procoagulant activity (PPA) was found by several methods, including tests of factor 3 availability (PF-3a), prothrombin consumption and contact activation. No deficiencies of platelet adhesion, aggregation, secretion, metabolism or granule-bound substances were detectable. Under adequate platelet coverage, this woman underwent two surgical procedures without difficulty. These findings demonstrate the role of PPA in hemostasis and indicate that a defect in PPA can be an isolated occurrence. The abnormalities in PF-3a found in this patient could be due to the diminished number of factor V binding sites, resulting in impaired factor Xa binding, found in separate studies by Majerus et al.

Evidence that platelet alpha-granules are a major determinant of platelet density: studies in storage pool deficiency.

Density-related subpopulations of platelets were obtained by centrifuging platelets obtained from venous blood on a discontinuous gradient of arabinogalactan (Stractan). Four subpopulations were obtained in fractions of the gradient with densities less than or equal to 1.058, 1.065, 1.070, and 1.092 g/ml. The percentage of the total platelet population recovered in these various fractions in 5 patients with congenital storage pool deficiency who are deficient only in dense granules (delta-SPD) was similar to that observed in 8 normal subjects. In contrast, a shift in the density distribution towards a higher percentage of less dense platelets was observed in 3 patients (alpha delta-SPD) who are deficient in both alpha and dense granules. The results of these studies strongly suggest that alpha-granules are a major determinant of platelet density.

Effect of aspirin and dipyridamole on the interaction of human platelets with sub-endothelium: studies using citrated and native blood.

The effect of aspirin and dipyridamole ingestion on the interaction of platelets with the subendothelium was studied using both citrated blood and directly sampled (native) blood. After obtained control studies, normal human subjects ingested 0.6 g of aspirin, 150 mg of dipyridamole, or a placebo and studies were repeated 1 1/2 hrs later. Subjects continued on placebo, aspirin (0.6 g b.i.d.) or dipyridamole (100 mg q.i.d.) for 6 days and studies were obtained 1 1/2 hrs after the last dose. Blood was circulated through an annular chamber on whose inner core were mounted everted segments of de-endothelialized rabbit aorta. The wall shear rate was 2,600 sec(-1). Surface coverage with adherent platelets and platelet thrombi, as well as several parameters of thrombus dimensions, were evaluated morphometrically. Aspirin ingestion markedly reduced platelet thrombi in citrated blood,--but had a much lesser inhibitory effective in native blood. Platelet adhesion was unaffected in native blood, in contrast to previous findings in which a lower shear rate (800 sec (-1)) was used. Ingestion of dipyridamole did not inhibit platelet adhesion or thrombi in either citrated or native blood. The studies indicated that, with the flow conditions used, aspirin is a relatively weak inhibitor of platelet thrombus formation in directly sampled human blood.

Release of human platelet factor V activity is induced by both collagen and ADP and is inhibited by aspirin.

Factor V activity in suspensions of human platelets washed by albumin density gradient separation increased in response to stimulation by both collagen and adenosine diphosphate (ADP). The appearance of factor V activity extracellularly had the characteristics of platelet secretion and was partially inhibited by aspirin and by the antimetabolites 2-deoxyglucose and antimycin A. Some increase in factor V activity was also observed in platelet suspensions during the initial response to ADP; this activity was not detected extracellularly, but remained associated with the platelets. Patients with storage pool deficiency (SPD) whose platelets are deficient only in dense granule substances released normal amounts of factor V activity, whereas decreased amounts were released in a patient whose platelets have both dense and alpha granule deficiencies. These findings suggest that a portion of platelet factor V is associated with, and released from, alpha granules.

Fibrin formation, fibrinopeptide A release, and platelet thrombus dimensions on subendothelium exposed to flowing native blood: greater in factor XII and XI than in factor VIII and IX deficiency.

Fibrin deposition and platelet thrombus dimensions on subendothelium were studied in four groups of patients with coagulation factor deficiencies. Five patients with factor VIII deficiency (APTT 120 +/- 8 sec) and three patients with factor IX deficiency (APTT 125 +/- 11 sec) were severe bleeders, whereas four patients with factor XII deficiency and seven with factor XI deficiency were either asymptomatic or only mild bleeders despite APTT values of 439 +/- 49 and 153 +/- 13 sec, respectively. Everted segments of deendothelialized rabbit aorta were exposed at a shear rate of 650 sec(-1) for 5 and 10 min to directly sampled venous blood in an annular chamber. Blood coagulation was evaluated by measuring fibrin deposition (percent surface coverage) on the subendothelium and post-chamber fibrinopeptide A levels; platelet thrombus dimensions on the subendothelium were evaluated by determining the total thrombus volume per surface area (using an optical scanning technique) and the average height of the three tallest thrombi. Consistent differences were observed among the patient groups for both the 5-min and 10-min exposure times. The larger of the 5- and 10-min exposure-time values was used to calculate group averages. Fibrin deposition in normal subjects was 81% +/- 5% surface coverage, and post-chamber fibrinopeptide A values were 712 +/- 64 ng/ml. Markedly decreased fibrin deposition and fibrinopeptide A levels were observed in factor VIII deficiency (2% +/- 1% and 102 +/- 19 ng/ml) and factor IX deficiency (11% +/- 7% and 69 +/- 11 ng/ml). In contrast, significantly higher values were obtained in patients deficient in factor XI (33% +/- 5% and 201 +/- 57 ng/ml) and factor XII (66% +/- 12% and 306 +/- 72 ng/ml). Differences in thrombus dimensions were also observed. In normal subjects, the value for thrombus volume and average height of the tallest thrombi were 8.3 +/- 1.3 cu micron/sq micron and 145 +/- 11 micron, respectively, and in patients were as follows: FVIII, 2.7 +/- 0.6 and 71 +/- 7; FIX, 4.5 +/- 1.8 and 88 +/- 14; FXI, 11.8 +/- 1.9 and 125 +/- 10; and FXII, 7.9 +/- 3.1 and 130 +/- 25. Platelet thrombus dimensions were normal in a patient with fibrinogen deficiency, indicating that the smaller thrombi in factor VIII and factor IX deficiencies were probably due to impaired evolution of thrombin rather than diminished fibrin formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Severe aortic stenosis in a patient with recurrent gastrointestinal bleeding: replacement of the aortic valve with a porcine xenograft.

Patients with aortic stenosis are subject to recurrent episodes of gastrointestinal bleeding of uncertain cause. How such patients should be handled when aortic valve replacement is required is not established. This report deals with such a patient who underwent successful aortic valve replacement with a porcine xenograft without anticoagulation. The patient has had no recurrent gastrointestinal bleeding since the valve replacement. The use of the now widely available porcine xenograft for aortic valve replacement avoids the need for anticoagulants in patients with a history of recurrent gastrointestinal bleeding. This case and limited data from the medical literature suggest that recurrent gastrointestinal bleeding after aortic valve replacement may be uncommon.

Platelets and surface-mediated clotting activity.

In contrast to previously reported studies, no evidence could be adduced for the activation of Hageman factor (factor XII) by platelets, whether or not these cells had been incubated with adenosine diphosphate (ADP).

Homeless persons and health care.

Health care is generally unavailable for the homeless. This heterogeneous group of men and women, including long-term street dwellers, residents of shelters, the chronically mentally ill, the economically debased, and alienated youth, are subject to a broad range of acute and chronic diseases, intensified by unsuitable living conditions, stress, and sociopathic behavior. Trauma, pulmonary tuberculosis, infestations, and peripheral vascular disease are common problems among the homeless; incomplete and fragmentary medical care permits exacerbation of chronic disorders. Outreach programs imaginatively constructed by teams of physicians, nurses, and social workers can effectively reestablish and maintain health services for these disenfranchised persons.

Pseudo-von Willebrand's disease. An intrinsic platelet defect with aggregation by unmodified human factor VIII/von Willebrand factor and enhanced adsorption of its high-molecular-weight multimers.

Four members (from four generations) of a family with a mild bleeding disorder and intermittent thrombocytopenia had decreased plasma levels of properties related to factor VIII/von Willebrand factor (FVIII/VWF), an absence of high-molecular-weight forms of FVIII/VWF in the plasma (but normal multimeric structure in the platelets), and increased ristocetin-induced platelet aggregation, as in Type IIB von Willebrand's disease. However, unlike the abnormality in FVIII/VWF in Type IIB disease, the basic defect in this family was in their platelets, which absorbed FVIII/VWF high-molecular-weight multimers at lower concentrations of ristocetin than did normal platelets. In addition, either in platelet-rich plasma or suspended in buffer, their platelets were aggregated by unmodified normal human FVIII/VWF without ristocetin. Since the abnormalities of plasma FVIII/VWF in this family may be secondary to the platelet abnormalities, the term "pseudo-von Willbrand's disease" may be suitably descriptive of their disorder.