Presence Of Thrombocytopenia Research Articles

Increased thromboxane biosynthesis in childhood hemolytic uremic syndrome

Vascular endothelial cell damage plays a central role in the pathogenesis of the hemolytic uremic syndrome (HUS), resulting in intravascular platelet activation and thrombotic microangiopathy. A deficiency of the antiaggregatory prostacyclin (PGI2) has been postulated by experiments under ex vivo conditions. However, this observation has not been confirmed in vivo. The pathophysiological contribution of thromboxane (Tx)A2, a potent vasoconstrictor and platelet-aggregating prostanoid which is predominantly produced by platelets, has not been elucidated so far. In order to quantitate endogenous formation of TxA2 in children with HUS, plasma concentrations of the enzymatic metabolite 11-dehydro-TxB2 of TxA2 and urinary excretion rates of three major TxA2 metabolites, TxB2, 11-dehydro-TxB2 and 2,3-dinor-TxB2 were analyzed using gas chromatography/mass spectrometry. PGI2 biosynthesis was assessed by measuring urinary excretion of an index metabolite of its systemic production, 2,3-dinor-6-keto-prostaglandin (PG) F1 alpha, and an index of its renal production, 6-keto-PGF1 alpha. TxA2 biosynthesis was markedly elevated in the acute phase of HUS. This activation could be detected for a longer period of time than the presence of thrombocytopenia. Concomitantly in the acute phase, renal PGI2 formation was significantly elevated and systemic PGI2 formation was elevated in 50% of the patients. These data indicate that TxA2 formation is increased in the acute phase in patients with HUS. This enhanced biosynthesis is consistent with increased platelet activation, whereas the increased PGI2 biosynthesis reflects predominantly renal endothelial cell damage.

Intravascular platelet activation in the hemolytic uremic syndrome

We studied intravascular platelet activation in patients with typical (epidemic) and atypical (sporadic) HUS and found defective aggregation, decreased platelet and increased plasma serotonin in both groups. The findings were present not only on admission during the thrombocytopenic stage of the disease, but persisted for several weeks after recovery of the platelet count. Reduced endothelial PGI2 production was significantly more common in plasma from atypical than typical cases. Plasma from both typical and atypical HUS patients induced aggregation of normal platelets, but this phenomenon was unrelated to both the presence of thrombocytopenia or the stage of the disease. Serum platelet aggregating activity was higher in the atypical HUS patients, and was not associated with immune complexes detectable by polyethylene glycol precipitation. The data indicate that intravascular platelet activation is a feature of both forms of HUS, and may be initiated by different mechanisms in the two subgroups. While abnormal PGI2 synthesis appears to be important in the atypical cases, neither defective PGI2 production nor platelet aggregation by plasma factors adequately accounts for platelet activation in the majority of typical cases.

Thrombocytopenia in patients with aortopulmonary transposition and an intact ventricular septum.

Relations between platelet counts and mean pulmonary arterial pressures, capillary oxygen tension, and haematocrit were studied in 37 patients, aged 2 to 16 months, with simple aortopulmonary transposition (an intact ventricular septum and no ductus arteriosus). There was a statistically significant inverse relation between pulmonary arterial pressures and platelet counts. Six out of the eight patients (4-16 months old) with raised mean pulmonary arterial pressure had thrombocytopenia (less than 100,000/mm3) and none of the 25 patients with a normal mean pulmonary pressure (less than or equal to 20 mm Hg) showed thrombocytopenia. Pulmonary arterial pressures were not measured in four patients: the platelet count was 7000/mm3 in the patient with a left ventricular systolic pressure of 90 mm Hg but it was greater than 100,000/mm3 in the three in whom left ventricular systolic pressure was less than 50 mm Hg. Platelet counts were positively correlated with capillary oxygen tension and inversely correlated with haematocrit in all 37 patients. Despite the persistence of pulmonary hypertension, thrombocytopenia improved after corrective surgery in five patients, even in those who had thrombocytopenia before operation. These data suggest that the presence of thrombocytopenia is not solely related to the development of pulmonary vascular disease. Pulmonary vascular disease, however, does contribute to the early development of thrombocytopenia in patients with simple aortopulmonary transposition.

ISOLATION OF HIV FROM HEMOPHILIACS

As part of a prospective study of human immunodeficiency virus (HIV) infection in hemophiliacs, peripheral blood mononuclear cells from 72 individuals without AIDS or ARC were cultured for virus. HIV was isolated from 15 out of 66 (23%) of hemophiliacs who were seropositive for HIV, and 0 of 6 seronegative patients. Virus isolation-positive hemophiliacs had significantly (p<.05) reduced T-helper cell numbers, T-helper/T-suppressor ratios, pokeweed mitogen responsiveness and total platelet counts when compared to seropositive hemophiliacs who did not yield HIV upon cultivation. One virus-positive patient has developed AIDS during the study period but no other virus-positive or negative hemophiliac has yet developed ARC or AIDS. Virus isolation-positive hemophiliacs did not differ from virus isolation-negative hemophiliacs in their HIV neutralizing antibody titers. Five of six HIV isolation-positive hemophiliacs were again successfully cultured for virus at later dates ranging from 3-12 months. Nine virus negative individuals remained virus negative when re-cultured at later dates. These data suggest that a significant subgroup of HIV seropositive hemophiliacs persistently harbor live virus and that seropositivity is a valid indication of virus infection. The significant decrease in the number of T-helper cells and the presence of thrombocytopenia in the isolation-positive group may be a reflection of a heavier virus load, and might be an early marker of more significant disease.

Heparin-Associated Thrombocytopenia

We studied the mechanism of platelet injury in 20 patients receiving heparin, three of whom became thrombocytopenic. Platelets from these three patients had increased levels of IgG and C3, which correlated with the presence of thrombocytopenia; their plasma caused the release of serotonin from normal platelets at concentrations of heparin within the usual therapeutic range. This reaction required IgG and an intact classic complement pathway. The 17 patients receiving heparin in whom thrombocytopenia did not develop had normal levels of platelet-associated IgG and C3. Plasma from 14 of these patients caused the release of serotonin, but only at heparin concentrations above the therapeutic range, in a reaction that also required IgG and complement. The addition of heparin to 15 normal plasma samples did not cause platelet injury in vitro. These studies indicate that heparin administration can be associated with complement-mediated platlet injury. The dose-dependent nature of this process may account for the occurrence of thrombocytopenia in some of these patients.

Phlebitis associated with the intravenous use of cephapirin and cephalothin in the combination therapy of antibiotics.

Phlebitis related to antibiotic infusion is one of the most frequent causes of morbidity in the debilitated patients with severe infection. There are a number of causes of infusion-induced phlebitis such as pH of intravenous fluid, needle used, and contamination of venipuncture site. Vein used to play an important role, particularly in patients with granulocytopenia receiving intravenous infusion. Cephalothin is an effective antibiotic in the treatment of granulocytopenic infection and is widely used currently. When cephalothin was introduced commercially, the frequency of phlebitis was as high as 50%. The main reason was thought to be acidity of the antibiotic solution. The cephalothin solution used currently is neutral in pH, but prevention of phlebitis is still not perfect. In contrast, cephapirin recently developed cephalosporin antibiotic, which resembles cephalothin in the antimicrobial activity and pharmacological properties caused less phlebitis than cephalothin in initial clinical studies. The patients receiving chemotherapy for malignant diseases frequently die of infections. A cephalosporin antibiotic is administered intravenously for a prolonged time in the presence of thrombocytopenia, and under such circumstances, other antibiotics such as carbenicillin (CBPC) and aminoglycoside are usually used in combination. The influence of these antibiotics injected through the same vein must be considered, but the possibility of phlebitis due to CBPC and aminoglycoside is negligible. In the present clinical study, 24 granulocytopenic patients were treated with the combination of antibiotics, cephapirin-carbenicillin-amikacin and cephalothin-carbenicillin-amikacin. Besides the clinical effect of the antibiotics, the incidence and severity of phlebitis were studied.

Sodium valproate and thrombocytopenia

Thrombocytopenia has been occasionally reported in patients on sodium valproate. Here is reported a 6-year-old boy on this drug who was found to have thrombocytopenia 6 months after initiation of administration and it was progressive up to 16 months. Though the medication was continued because of its efficacy, platelet count gradually recovered to the normal level spontaneously. Throughout the course, no hemorrhagic tendency was observed clinically. It was suggested that platelet count should be monitored periodically, but that the presence of thrombocytopenia itself does not serve as an absolute indication for discontinuing the drug.

Thrombophlebitis in Systemic Lupus Erythematosus

Thrombophlebitis occurred in 14 (12.2%) of 114 patients with active systemic lupus erythematosus (SLE). Abnormal clotting occurred despite the presence of thrombocytopenia or circulating anticoagulants in some of the patients, and the development of pulmonary emboli was verified in seven. Although infrequently reported, the association of thrombophlebitis with active SLE is apparently not uncommon. While there were no features that distinguished this group of patients from other groups of patients with SLE, there are some possible mechanisms. Recognition of this complication of SLE is important because of the frequent occurrence of SLE-induced pleuritis and its similarity to the pain of pulmonary emboli.

Spurious Elevation of the Platelet Count in Acute Leukemia

SYMPTOMS of acute leukemia are usually related to the absence of normal hemopoiesis. Bleeding related to thrombocytopenia and infection secondary to neutropenia are the most serious manifestations. Before the advent of platelet transfusions, bleeding was the most common cause of death in acute leukemia.¹More recently with the increasing availability of platelet transfusions and the ability to supply HLA-matched platelets, infection has replaced bleeding as the major cause of death.²However, for platelet transfusions to have an impact on survival, the presence of thrombocytopenia must be recognized. In the case reported here, the recognition that bleeding symptoms were secondary to thrombocytopenia was delayed because of artifactually elevated platelet counts due to circulating fragments of leukemic cells. <h3>Report of a Case</h3> A 49-year-old farmer in whom leukemia had been diagnosed, had noticed increasing fatigue for six months and had been hospitalized locally one week earlier with pneumonia. His condition

LACK OF THROMBOCYTOPENIA IN NEWBORN INFANTS TREATED WITH PHOTOTHERAPY

Recent investigations in animals and in low birthweight infants showed that conventional phototherapy increases the rate of platelet turnover. A prospective study was designed to investigate the time relationship between clinical signs of neonatal sepsis, detection of thrombocytopenia and positive blood culture. As part of the same study we investigated the effect of conventional phototherapy on platelet counts. Sixty newborn infants who had septic work-up but without positive blood culture and without a clinical condition known to cause thrombocytopenia were included in this study. Platelet counts by phase microscopy were done at the time of septic work-up and repeated at 12, 24, 48 and 72 hours. Twenty-four infants received phototherapy during the study period (mean 48 ± 25 S.D. hours) and 36 served as controls.None of the infants of phototherapy or control group developed thrombocytopenia (platelets <100,000/mm3)neither statistical comparisons between the two groups, at the above time intervals, showed any significant differences. Contrary to previous reports this study does not show any thrombocytopenia associated with conventional phototherapy although the platelet turnover may be increased. In the presence of thrombocytopenia, etiology other than phototherapy should be considered.

Classification of chronic myelocytic leukemia in children.

The present study was undertaken to define criteria for classification of chronic myelocytic leukemia in children and adolescents. From April, 1963 through July, 1971, 18 patients were available for study. Evaluation of the clinical, laboratory, and histopathologic features demonstrates three distinct subgroups: adult, juvenile, and familial chronic myelocytic leukemia. Parameters of most value in this distinction are the level of the white blood cell count, presence of thrombocytopenia or thrombocytosis, the bone marrow myeloid to erythroid ratio, and the presence or absence of well-defined malpighian corpuscles in the spleen. One patient with acute lymphocytic leukemia in remission manifested some unique features and may represent a fourth form of chronic myelocytic leukemia, resulting from previous chemotherapy or irradiation. The use of chemotherapy has not significantly prolonged survival in our patients. Two patients with familial chronic myelocytic leukemia are surviving in remission 9 years following splenectomy.

Platelet Changes Following Clinical And Experimental Hepatic Homotransplantation

DURING the last four years, ten patients with liver disease have been treated at the University of Colorado with either orthotopic or auxiliary hepatic homotransplantation. 1,2 A hemorrhagic diathesis, explained at least partially by increased circulating fibrinolysins, 3 frequently complicated the operative procedure. Derangements in other clotting factors are also known to occur, 3,4 but the presence of thrombocytopenia during the early postoperative period has not been well documented. In the present study, platelet changes in the clinical cases are reviewed. In addition, the magnitude, timing, and duration of thrombocytopenia have been evaluated under controlled circumstances in untreated dogs subjected to orthotopic transplantation, as well as in comparable experiments in which various immunosuppressive agents were provided including antilymphocyte globulin, azathioprine, and prednisone. Methods Clinical Studies.— Three attempts at auxiliary transplantation were performed: One patient died two hours after operation and the other two lived for 22 and 34 days, respectively.

Liver Biopsy and Splenoportography in Patients with Thrombocytopenia

Summary Eighteen patients are described in whom liver biopsy or splenoportography, or both, was performed, without complications, in the presence of thrombocytopenia. With adequate safeguards, we would suggest that the morbidity of liver biopsy or splenoportography in the presence of thrombocytopenia need not be regarded as prohibitive.

Independence of Protamine Titration and Platelet Level in Certain Hemorrhagic Diseases.

Summary1. The platelet concentration influences the sensitivity of bloods and plasmas to the effect of added heparin. The anticoagulant potency of heparin is also enhanced by prothrombin deficiency. The potentiated effect of heparin in thrombocytopenic bloods may be due to reduced thromboplastin (cephalin) activity.2. The protamine titration may be increased when the platelet count is normal and it may be normal in the presence of thrombocytopenia. It is influenced by heparin, heparinoid substances, prothrombin deficiency, hemophilia, and possibly other factors.3. Increased protamine titrations may occur in bleeding patients who have no other apparent clotting defects, including the whole blood clotting time. Many of these patients cease bleeding when given intravenous toluidine blue. The protamine titration under these conditions can be returned to or toward normal regardless of the platelet level.