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Biomedical subjects

C P Hayward

Publications and source records attributed to C P Hayward.

At least 19 recordsLinked to original sources
PubMed2001

Decreased von Willebrand factor protease activity associated with thrombocytopenic disorders.

Recent studies investigating thrombotic thrombocytopenic purpura (TTP) have implicated abnormal plasma von Willebrand factor (vWF)-cleaving metalloprotease activity in this disorder. It has been proposed that a metalloprotease cleaves unusually large (UL) multimers of vWF, which enter the circulation from the endothelium. Abnormal metalloprotease activity could result in ULvWF, which could participate in TTP. However, the diagnostic specificity of abnormalities in the plasma metalloprotease activity has not been established. A prospective study of vWF protease activity was performed using samples from 20 healthy controls, 20 patients with acute TTP, 20 patients with immune idiopathic thrombocytopenic purpura (ITP), 10 patients with disseminated intravascular thrombocytopenia (DIC), 10 patients with systemic lupus erythematosus (SLE,) and 5 thrombocytopenic patients with leukemia. Studies were performed blinded to the diagnosis. Samples from hospitalized patients with normal platelet counts were also tested. The vWF digests and multimer analysis were done using previously described methods. Six laboratory personnel independently scored each of the multimer gels. Reduced protease activity was observed in 9 of 20 patients with TTP. Reduced activity was also observed in 6 of 20 patients with ITP, 6 of 10 patients with DIC, 5 of 10 patients with SLE, 1 of 5 patients with leukemia, 2 of 20 healthy controls, and 3 of 25 hospitalized patients. This study indicates that abnormalities of vWF protease activity are not restricted to patients with the diagnosis of TTP.

Disseminated Intravascular Coagulation↗
PubMed2001

Platelets from patients with the Quebec platelet disorder contain and secrete abnormal amounts of urokinase-type plasminogen activator.

The Quebec platelet disorder (QPD) is an autosomal dominant platelet disorder associated with delayed bleeding and alpha-granule protein degradation. The degradation of alpha-granule, but not plasma, fibrinogen in patients with the QPD led to the investigation of their platelets for a protease defect. Unlike normal platelets, QPD platelets contained large amounts of fibrinolytic serine proteases that had properties of plasminogen activators. Western blot analysis, zymography, and immunodepletion experiments indicated this was because QPD platelets contained large amounts of urokinase-type plasminogen activator (u-PA) within a secretory compartment. u-PA antigen was not increased in all QPD plasmas, whereas it was increased more than 100-fold in QPD platelets (P <.00009), which contained increased u-PA messenger RNA. Although QPD platelets contained 2-fold more plasminogen activator inhibitor 1 (PAI-1) (P <.0008) and 100-fold greater u-PA-PAI-1 complexes (P <.0002) than normal platelets, they contained excess u-PA activity, predominantly in the form of two chain (tcu-PA), which required additional PAI-1 for full inhibition. There was associated proteolysis of plasminogen in QPD platelets, to forms that comigrated with plasmin. When similar amounts of tcu-PA were incubated with normal platelet secretory proteins, many alpha-granule proteins were proteolyzed to forms that resembled degraded QPD platelet proteins. These data implicate u-PA in the pathogenesis of alpha-granule protein degradation in the QPD. Although patients with the QPD have normal to increased u-PA levels in their plasma, without evidence of systemic fibrinogenolysis, their increased platelet u-PA could contribute to bleeding by accelerating fibrinolysis within the hemostatic plug. QPD is the only inherited bleeding disorder in humans known to be associated with increased u-PA.

Blood Platelet Disorders↗
PubMed2001

Platelet factor V New York: a defect in factor V distinct from that in factor V Quebec resulting in impaired prothrombinase generation.

Studies were performed on a patient with a longstanding bleeding disorder whose major defects were impaired platelet prothrombinase activity in the absence of added factor Va, and a platelet factor V value that was either decreased or at the lower limit of normal when assayed on multiple occasions. In contrast, plasma factor V values were consistently normal. Unlike Scott Syndrome, in which platelet prothrombinase activity is decreased in both the presence and absence of added factor V, her platelets appeared to utilize added factor Va normally in supporting the generation of prothrombinase activity. These findings suggest an intrinsic defect in platelet factor V as the basis of her platelet prothrombinase defect. This defect appears to be different than that described in the Quebec platelet disorder (factor V Quebec). Immunoblot analyses of washed platelet lysates demonstrated a pattern of variably sized factor V molecules that was entirely similar to that observed in normal platelets, and both the heavy and light chains of her factor V after thrombin cleavage were of the same size as that observed in normal platelets. In addition, her platelet multimerin was normal and immunoblot analysis excluded the type of generalized granular protein defect and pathological proteolysis that has been suggested to explain the factor V defect in the Quebec platelet disorder. The findings in this patient thus suggest a new type of platelet factor V defect as the basis for the impaired capacity of her activated platelets to support prothrombinase generation. The findings further support an important role for platelet factor V in hemostasis.

Blood Coagulation Factors↗
PubMed2001

The storage defects in grey platelet syndrome and alphadelta-storage pool deficiency affect alpha-granule factor V and multimerin storage without altering their proteolytic processing.

Among proteins stored in alpha-granules, multimerin and factor V share unusual features: they bind to each other, are proteolysed to unique forms and are stored eccentrically in alpha-granules. These unique features of their processing led us to study these proteins in alpha delta storage pool deficiency (alphadelta-SPD) and grey platelet syndrome (GPS, alpha-SPD), two conditions known to impair alpha-granule protein storage. Platelet factor V and multimerin were severely reduced in GPS, whereas they ranged from reduced to normal in alphadelta-SPD. The platelet levels of factor V and multimerin in these disorders indicated multimerin deficiency was not predictive of platelet factor V deficiency, although it reduced the amount of multimerin associated with platelet factor V. In GPS only, the defect in storing proteins was associated with increased multimerin and multimerin-factor V complexes in plasma. Like normal platelets, GPS and alphadelta-SPD platelets contained factor V mainly in granules. Platelet factor V and multimerin were proteolysed to normal platelet forms in GPS and alphadelta-SPD platelets, indicating that these conditions preserve some aspects of normal alpha-granule protein processing. Although we found factor V can be stored in platelets deficient in multimerin, our data indicate that multimerin storage influences the point at which multimerin binds factor V.

Blood Platelets↗
PubMed2000

Morphological analysis of microparticle generation in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) with thrombosis is a serious complication of heparin use. HIT sera can generate platelet-derived microparticles, which are produced in a heparin-dependent manner and are hypothesized to be important initial pathological participants because they promote vascular occlusion. To date, microparticles have been studied using flow cytometric techniques. However, it is uncertain whether the small-sized material seen in flow cytometric studies represents true platelet microparticles shed from activated platelets or whether they are platelets that have contracted after releasing their internal components. This report describes a morphological investigation of platelet-derived microparticles in HIT using, among other techniques, confocal, scanning electron, and transmission electron microscopy. Following incubation with HIT sera, the existence of small membrane-bound vesicles in the milieu of activated platelets was demonstrated. A population of microparticles, expressing platelet-specific glycoproteins, was separated from platelets by centrifugation over a sucrose layer. These microparticles had identical flow cytometric profiles, size heterogeneity, and GPIb(alpha) and GPIIb/IIIa staining intensity as the microparticle population in unfractionated samples. When microparticles were generated in situ and fixed onto grids, they were demonstrated to be distinct membrane-bound vesicles that originated near the platelet body and terminal ends of pseudopods on activated platelets. These microparticles appeared to be generated by localized swelling, budding, and release. Collectively, these morphological studies document the existence of true microparticles in platelets activated by HIT sera. The microparticles may play an important role in the pathogenesis of HIT.

Anticoagulants↗
PubMed2000

Loss of factor VIII activity during storage in PVC containers due to adsorption.

Recombinant factor VIII concentrates are stable when administered in a reconstituted form according to the manufacturer's specifications, and undiluted via infusion with syringe mini-pumps. However many Haemophilia centres administer recombinant factor VIII further diluted in intravenous fluids for greater ease of administration. To investigate the stability of recombinant factor VIII during administration as a diluted infusion, reconstituted factor VIII was stored in polyvinylchloride (PVC) mini-bags undiluted (146 IU mL-1) and at factor VIII concentrations of 10 IU mL-1 and 2 IU mL-1. After 48 h of storage at room temperature in PVC mini-bags, the recoveries of factor VIII activity were 41.9% of the initial activity for the undiluted (146 IU mL-1) product and 43.7% of the initial activity for factor VIII diluted to 10 IU mL-1. For factor VIII diluted to 2 IU mL-1, the amount of factor VIII activity remaining at 48 h was only 1.8% of the initial activity. In contrast, 100% of factor VIII activity was recovered after 48 h when undiluted reconstituted product (146 IU mL-1) was stored in a syringe. To investigate the mechanism of factor VIII activity loss during storage, factor VIII samples collected after 0, 3 and 48 h of storage were analysed by immunoblotting with factor VIII antibodies. No evidence of factor VIII proteolytic degradation during storage was found, however, large amounts of factor VIII antigen were recovered from the empty PVC mini-bags following elution with denaturing detergent. We conclude that clinically significant losses of factor VIII activity occur during storage in PVC mini-bags and that the loss of activity is most likely due to protein adsorption onto the plastic surface. This loss of factor VIII activity during storage in PVC containers may substantially affect the safety and potential cost savings of administering recombinant factor VIII by continuous infusion.

Adsorption↗
PubMed1999

Multimerin processing by cells with and without pathways for regulated protein secretion.

Multimerin is a massive, soluble, homomultimeric, factor V-binding protein found in platelet alpha-granules and in vascular endothelium. Unlike platelets, endothelial cells contain multimerin within granules that lack the secretory granule membrane protein P-selectin, and in culture, they constitutively secrete most of their synthesized multimerin. To further evaluate multimerin's posttranslational processing and storage, we expressed human endothelial cell prepromultimerin in a variety of cell lines, with and without pathways for regulated secretion. The recombinant multimerin produced by these different cells showed variations in its glycosylation, proteolytic processing, and multimer profile, and human embryonic kidney 293 cells recapitulated multimerin's normal processing for constitutive secretion by human endothelial cells. When multimerin was expressed in a neuroendocrine cell line capable of regulated protein secretion, it was efficiently targeted for regulated secretion. However, the multimerin stored in these cells was proteolyzed more extensively than normally occurs in platelets, suggesting that endoproteases similar to those expressed by megakaryocytes are required to produce platelet-type multimerin. The impact of the tissue-specific differences in multimerin's posttranslational processing on its functions is not yet known. Multimerin's sorting and targeting for regulated secretion may be important for its functions and its association with factor V in secretion granules.

Blood Platelets↗
PubMed1999

Serum-induced platelet procoagulant activity: an assay for the characterization of prothrombotic disorders.

Platelets contribute to hemostasis by forming a platelet plug and by providing a procoagulant surface for the assembly and activation of the coagulation factors. The contribution of platelets to prothrombotic disorders has been difficult to analyze. Recently an assay was reported that measured the procoagulant activity of test platelets by making the platelet lipid surface the limiting factor in the production of thrombin. In this report we describe a novel technique, based on this assay, that we used to study patient serum factors that activate control platelets and in turn initiate measurable procoagulant activity. Using this assay we investigated a group of patients with prothrombotic disorders. The patient test serum was incubated with normal platelets in the presence of activated factor Xa. The resultant thrombin was measured in a chromogenic assay. The rate-limiting step was the presence of any potential platelet-activating factors, such as antibodies in the heat-treated test serum, that would allow the Xa to bind to the platelet phospholipid surface. Serum samples from patients with heparin-induced thrombocytopenia (HIT) and the anti-phospholipid antibody syndrome enhanced platelet procoagulant activity, while samples from patients with idiopathic thrombocytopenic purpura and disseminated intravascular coagulation (DIC) did not. HIT serum samples also induced platelet activation, as measured by platelet microparticle shedding, carbon 14-labeled serotonin release, and platelet aggregation. The measurement of serum-induced platelet procoagulant activity provides a method for the investigation of circulating platelet agonists in prothrombotic disorders.

Antiphospholipid Syndrome↗
PubMed1999

Measurement of endogenous and exogenous alpha-granular platelet proteins in patients with immune and nonimmune thrombocytopenia.

Idiopathic thrombocytopenic purpura (ITP) is caused by antiplatelet antibodies and is characterized by increased platelet destruction and elevated levels of IgG (platelet-associated IgG, PAIgG). Nonimmune thrombocytopenic patients also have elevated levels of PAIgG. In this study we investigated two possible biological explanations for the increased levels of PAIgG in these patients. The first hypothesis suggests that a thrombocytopenic stress causes increased thrombocytopoiesis with increased numbers and content of the platelet alpha granules. The second hypothesis is that for uncertain reasons (immunological or cytokine) there is increased absorption of plasma proteins by either megakaryocytes or by the platelets themselves. To address this issue, we compared the level of megakaryocyte synthesized alpha granular proteins [platelet factor 4 (PF4) and beta-thromboglobulin (beta-TG)] to plasma-absorbed alpha granular proteins (albumin, IgG and fibrinogen) in patients with immune (n = 39) and nonimmune (n = 60) thrombocytopenias. Plasma-absorbed alpha-granular proteins were elevated in both immune and nonimmune thrombocytopenia with no increase in megakaryocyte synthesized alpha-granular proteins. These plasma-derived protein elevations were not attributable to elevated mean platelet volumes or elevated plasma concentrations of the respective protein. We hypothesize that the increased IgG in these platelets is not the result of production of larger platelets, but reflects a selective increase in the endocytosis of plasma-absorbed alpha-granular proteins at the megakaryocyte and/or platelet level.

Albumins↗
PubMed1998

Studies of multimerin in human endothelial cells.

Multimerin is a novel, massive, soluble protein that resembles von Willebrand factor in its repeating, homomultimeric structure. Both proteins are expressed by megakaryocytes and endothelial cells and are stored in the region of platelet alpha-granules resembling Weibel-Palade bodies. These findings led us to study the distribution of multimerin within human endothelial cells. Multimerin was identified in vascular endothelium in situ. In cultured endothelial cells, multimerin was identified within round to rod-shaped, dense-core granules, some of which contained intragranular, longitudinally arranged tubules and resembled Weibel-Palade bodies. However, multimerin was found primarily in different structures than the Weibel-Palade body proteins von Willebrand factor and P-selectin. After stimulation with secretagogues, multimerin was observed to redistribute from intracellular structures to the external cellular membrane, without detectable accompanied secretion of multimerin into the culture media. In early passage endothelial cell cultures, multimerin was associated with extensive, fibrillary, extracellular matrix structures, in a different distribution than fibronectin. Although multimerin and von Willebrand factor are stored together in platelets, they are mainly found within different structures in endothelial cells, indicating that there are tissue-specific differences in the sorting of these soluble, multimeric proteins.

Blood Proteins↗
PubMed1998

ABH antigens on human platelets: expression on the glycosyl phosphatidylinositol-anchored protein CD109.

Platelets express alloantigens that are platelet specific (eg, the HPA antigens) and alloantigens that are shared with other blood cells (eg, the ABH antigens). The blood group A and B determinants are expressed on glycolipids and on some intrinsic platelet membrane glycoproteins. This report characterizes multiple platelet proteins reacting with blood group antibodies in serum samples from mothers of children born with neonatal alloimmune thrombocytopenia. ABH antigens on additional platelet proteins are identified, including the glycosyl phosphatidylinositol-anchored protein CD109. The proteins that carry ABH antigens were identified by using monoclonal antibodies to glycoproteins Ib, IIb/IIIa, Ia/IIa, CD31, and CD109 and immunoprecipitation/immunoblotting techniques with monoclonal antibodies to A and B antigens. The maternal serum samples and anti-A and anti-B monoclonal antibodies immunoprecipitated identical radiolabeled platelet proteins including proteins at 220 and 175 kd and proteins with mobilities corresponding to glycoproteins Ib, IIb/IIIa, IV, and V. Treatment of platelets with phosphatidylinositol-specific phospholipase C released into the supernatant a 175-kd protein that expressed the blood group determinants. This protein comigrated with the glycosyl phosphatidylinositol-anchored protein CD109. When platelet proteins were purified by immunoprecipitation with monoclonal antibodies and then tested by immunoblotting, anti-A reacted with the glycosyl phosphatidylinositol-anchored protein CD109 and to glycoproteins Ib, IIb, IIa, IIIa, and CD31 (PECAM). These results indicate that structures for modification by glycosyltransferases exist on platelet CD109, which also expresses the Gov alloantigen system. This study indicates that certain platelet proteins express both platelet-specific and blood group antigens that may contribute to platelet transfusion refractoriness and to neonatal alloimmune thrombocytopenia.

Animals↗
PubMed1998

Studies of multimerin in patients with von Willebrand disease and platelet von Willebrand factor deficiency.

In normal platelet alpha-granules von Willebrand factor (VWF) is stored with multimerin and factor V in an eccentric electron-lucent zone. Because the platelet stores of VWF are deficient in 'platelet low' type 1 and type 3 von Willebrand disease (VWD), we investigated their electron-lucent zone proteins. The patients with VWD had partial to complete deficiencies of plasma and platelet VWF but normal alpha-granular multimerin and factor V, and normal alpha-granular fibrinogen, thrombospondin-1, fibronectin, osteonectin and P-selectin. In type 3 VWD platelets, alpha-granular electron-lucent zones lacking VWF-associated tubules were identified and multimerin was found in its normal alpha-granular location. These findings indicate that the formation of the electron-lucent zone and the sorting of multimerin to this region occur independent of VWE The isolated abnormalities in VWF suggests a VWF gene mutation is the cause of 'platelet low' type 1 VWD.

Blood Platelets↗
PubMed1997

The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia.

BACKGROUND: Platelet-mediated arterial occlusion is a well-recognized cause of limb loss in patients with heparin-induced thrombocytopenia. However, the syndrome of distal ischemic necrosis complicating the deep venous thrombosis (venous limb gangrene) sometimes associated with heparin-induced thrombocytopenia has not been well characterized. OBJECTIVE: To study the pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia. DESIGN: Characterization (based on descriptive and case-control studies) of a novel syndrome of limb loss and hypothesis testing by analysis of plasma samples. SETTING: Five university-associated hospitals in one medical community. PATIENTS: Clinical and laboratory records of 158 patients with heparin-induced thrombocytopenia were reviewed to identify patients with venous limb gangrene (n = 8), limb arterial thrombosis (n = 10), and uncomplicated deep venous thrombosis (n = 58). MEASUREMENTS: Clinical and laboratory factors associated with venous limb gangrene, including thrombin-antithrombin complexes and vitamin K-dependent procoagulant and anticoagulant factors. RESULTS: Warfarin treatment was more frequently associated with venous limb gangrene than with limb arterial thrombosis (8 of 8 patients compared with 3 of 10 patients; P = 0.004). The anticoagulant effect of warfarin seemed greater in the 8 patients with venous limb gangrene than in the 58 patients who did not develop gangrene (median International normalized ratio, 5.8 compared with 3.1; P < 0.001). Compared with plasma from controls, plasma from patients with venous limb gangrene had a higher ratio of thrombin-antithrombin complex to protein C activity during warfarin treatment. No hereditable abnormalities of the protein C anticoagulant pathway were seen in any patient. CONCLUSIONS: Warfarin treatment of deep venous thrombosis associated with heparin-induced thrombocytopenia is a possible cause of venous limb gangrene, perhaps because of acquired failure of the protein C anticoagulant pathway to regulate thrombin generation.

Adult↗
PubMed1997

Studies of a second family with the Quebec platelet disorder: evidence that the degradation of the alpha-granule membrane and its soluble contents are not secondary to a defect in targeting proteins to alpha-granules.

We recently described a Quebec family with an autosomal dominant bleeding disorder characterized by mildly reduced-low normal platelet counts, an epinephrine aggregation defect, multimerin deficiency, and proteolytic degradation of several, soluble alpha-granular proteins. Similar clinical features led us to investigate a second family with an unexplained, autosomal dominant bleeding disorder. The affected individuals had reduced to normal platelet counts, absent platelet aggregation with epinephrine, and multimerin deficiency. Their platelet alpha-granular proteins factor V, thrombospondin, von Willebrand factor, fibrinogen, fibronectin, osteonectin, and P-selectin were proteolyzed and comigrated with the degradation products found in patients from the other family. However, their platelet albumin, IgG, external membrane glycoproteins, CD63 (a lysosomal and dense granular protein), calpain, and plasma von Willebrand factor were normal, indicating restriction in the proteins proteolyzed. Electron microscopy studies indicated preserved alpha-granular ultrastructure, despite degradation of soluble and membrane alpha-granular proteins. Immunoelectron microscopy studies of the patients' platelets indicated that fibrinogen, von Willebrand factor, P-selectin, multimerin, and factor V were within alpha-granules, with normal to reduced labeling for these proteins. Pathologic proteolysis of alpha-granular contents, rather than a defect in targeting proteins to alpha-granules, may be the cause of the protein degradation in the Quebec platelet disorder.

Adult↗
PubMed1997

Proteolytic degradation of high molecular weight kininogen in acute thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by thrombocytopenia and schistocytic haemolytic anaemia. The majority of patients have normal coagulation parameters including the activated partial thromboplastin time (APTT). An intracellular cysteine protease, calpain, has been found in the plasma of many patients with acute TTP, and we hypothesize that it participates in the pathogenesis of the disorder. However, certain aspects of the disorder remain unresolved. For example, high molecular weight kininogen (HK) is one of the primary plasma inhibitors of calpain, and it also can act as a substrate for calpain. Consequently, one might anticipate that the HK could be defective or altered in TTP. In this report we describe the analysis of HK in plasma from live patients with acute TTP and following recovery. The HK was studied immunogenically and functionally. We observed that the HK in plasma samples from patients with acute TTP was proteolysed. This degradation was not observed in remission samples from the same patients. However, both acute and remission TTP samples had normal HK coagulant activity (acute samples, x = 0.84 +/- 0.26 U/ml; remission samples, x = 0.89 +/- 0.21 U/ml; control samples, x = 0.87 +/- 0.05 U/ml). Although the TTP plasmas were able to inhibit calpain activity, less inhibition activity was found in the acute samples (acute: mean inhibition 71 +/- 2.4%; remission: mean 92 +/- 2.1%; control samples: mean 93 +/- 5.4%; P < 0.001). Normal HK treated with calpain also had reduced calpain inhibition capacity (mean 58%). This study suggests that although HK is proteolysed during acute TTP, the proteolysis occurs without a major loss in the coagulation function or depletion of the protease inhibitory activity of HK.

Acute Disease↗
PubMed1997

Fibrinogen degradation products in patients with the Quebec platelet disorder.

The Quebec platelet disorder is a serious bleeding disorder associated with proteolysis of alpha-granular proteins, including fibrinogen. We evaluated fibrinogen degradation product (FDP) assays as screening tests for this disorder. Patients with the Quebec platelet disorder (13/13) had elevated serum FDPs (P < 0.01) due to secreted degraded platelet fibrinogen, but normal plasma FDPs and D-dimers. Unrelated controls with bleeding disorders (32/34) had undetectable FDPs, and controls with FDPs due to disseminated intravascular coagulation (DIC) and other illnesses (11/11) had elevated FDPs in all assays (P < 0.01). Immunoblot analyses indicated plasma fibrinogen was normal in the Quebec patients and platelet FDPs were found in their platelet lysates, releasates and serum samples. Their platelet FDPs were not altered by treatment with fibrinolytic inhibitors and were different from the FDPs in DIC and in plasmin-digested fibrinogen. Tests for serum FDPs may provide a simple rapid way to screen for the Quebec platelet disorder.

Antifibrinolytic Agents↗
PubMed1997

Maternal immunization to Gov system alloantigens on human platelets.

BACKGROUND: Immunization to platelet alloantigens can occur during pregnancy or after the transfusion of blood components. Platelet alloantibodies can cause neonatal alloimmune thrombocytopenia and posttransfusion purpura. Transfusion-induced alloimmunization to a novel platelet alloantigen system, Gov, expressed on the 175-kDa glycosyl phosphatidylinositol-anchored platelet glycoprotein, CD109, was previously described. This report describes three unrelated patients who were alloimmunized to Gov(a) or Gov(b) during pregnancy. STUDY DESIGN AND METHODS: Platelets were typed by using radioimmunoprecipitation for HPA-1a, -3a, -5a, -5b, Gov(a), and Gov(b) and by polymerase chain reaction-restriction fragment length polymorphism for HPA-1a, -1b, -3a, and -3b. Maternal sera were screened for platelet antibodies by using radioimmunoprecipitation and the antigen capture assay. RESULTS: Patients 1 and 2 were investigated after the diagnosis of neonatal alloimmune thrombocytopenia in their children, and alloantibodies specific for Gov(b) and Gov(a), respectively, were detected in maternal serum. Serum from patient 3, who had mild idiopathic thrombocytopenia purpura with no detectable autoantibody, was found to contain alloantibodies to Gov(b) and to HPA-5b, presumably as a result of immunization during pregnancy. Platelet typings confirmed that the patients were at risk for alloimmunization to the respective antigen. CONCLUSION: This report of three cases of maternal alloimmunization to antigens in the Gov system indicates that immunization can occur via placental transfer of antigen and that Gov system alloantibodies may be associated with neonatal alloimmune thrombocytopenia.

Adult↗