Thrombocytopenia following sustained-release procainamide

Procainamide hydrochloride-induced thrombocytopenia has infrequently been reported in the past. We report six cases of thrombocytopenia following the administration of the sustained-release form of procainamide. Three of these cases had platelet counts of less than 15,000/microL. The mean time to onset of thrombocytopenia from drug administration was 40 days (range, nine to 71 days). The mean time until normalization of the platelet counts after the drug therapy was stopped was 7.8 +/- 3.1 days (range, four to nine days). Oral prednisone therapy had little apparent benefit. The thrombocytopenia was not part of a systemic lupus erythematosus syndrome. We believe that thrombocytopenia is an important side effect of sustained-release procainamide therapy.     

Chronic thrombocytopenia in an immunodeficient patient with hemophilia A

Summary Coincident hemophilia and idiopathic thrombocytopenia has been rarely observed. We report here on a young man with severe hemophilia A who was treated with concentrates of lyophilized antihemophilic factor for several years before he developed thrombocytopenia. An isolated thrombocytopenia coincident with reduced platelet survival, ample megacaryocytes in the bone marrow, elevated platelet-associated IgG, as well as remission after treatment with prednisone and splenectomy, suggest the idiopathic form of thrombocytopenia. In addition, defects in cellular immunity became obvious. A causal relationship between the application of blood-derived products and the development of the platelet disorder as well as the impairment of the T-cell system remain to be demonstrated.     

Immunosuppressive treatment combined with nucleoside analog is superior to nucleoside analog only in the treatment of severe thrombocytopenia in patients with cirrhosis associated with hepatitis B in China: A multicenter,observational study

No effective treatment has been identified for patients of liver cirrhosis (LC) associated with hepatitis B virus (HBV) and severe thrombocytopenia. We aimed to explore the effectiveness and safety of low-dose prednisone or cyclosporine A (CsA) combined with nucleoside analog (NA) in patients with severe thrombocytopenia associated with HBV-related LC. We included 145 consecutive compensated HBV-associated LC patients with severe thrombocytopenia between 1 January 2006 and 31 December 2013. We divided the patients into three groups by treatment strategy, including NA only (n?=?57), NA plus prednisone (n?=?46), and NA plus CsA (n?=?42). We analyzed the platelet counts, bleeding events, liver function, replication of HBV, and outcomes in each group. At all time points during this observation, the platelet counts in prednisone or CsA group were higher than those in the NA only group. There are significant differences in the cumulative rates of bleeding events among the three groups. The platelet counts and treatment were factors associated with bleeding events in multivariate analysis. The differences in HBV-DNA negative rates, HBV-DNA elevated rates, normal serum alanine transaminase rates, serum alanine transaminase elevated more than two times the baseline rates, and HBeAg seropositive conversion ratio among the groups did not reach statistical significance. The adverse events in our study were, in general, mild and balanced among the three treatment groups. Treatment with low-dose prednisone or CsA plus NA could elevate the platelet counts and reduce the risk of bleeding events in HBV LC with severe thrombocytopenia.     

Danazol for lupus thrombocytopenia

Danazol therapy was used in the treatment of three consecutive patients with lupus-associated thrombocytopenia refractory to high-dose prednisone therapy (two patients) or in whom high-dose prednisone therapy was considered contraindicated (one patient). Treatment was associated in each case with an increase in platelet count but was complicated in two of three patients by the development of a diffuse maculopapular rash that promptly resolved following discontinuation of danazol therapy. Retreatment of one patient with danazol was associated with immediate recurrence of the rash. We suggest that danazol therapy deserves further evaluation in the treatment of lupus-associated thrombocytopenia, but advise that patients be carefully monitored for rash.     

Pseudo-Bernard-Soulier syndrome: thrombocytopenia caused by autoantibody to platelet glycoprotein Ib

The Bernard-Soulier syndrome is an inherited bleeding disorder that is due to a deficiency in platelet glycoprotein Ib. Bernard-Soulier platelets fail to agglutinate in response to ristocetin despite normal levels of factor VIII:von Willebrand factor. We report a patient who developed severe refractory thrombocytopenia postsurgically while receiving procainamide therapy. Thrombocytopenia was immune mediated since the patient's platelets bore high levels of antiplatelet antibody. Radioimmunoprecipitation studies demonstrated that the autoantibodies had specificity for platelet glycoproteins Ib and V as well as platelet HLA. The patient's plasma as well as purified immunoglobulin G completely inhibited the ristocetin-induced aggregation of normal platelets but did not inhibit adenosine diphosphate-induced aggregation. The laboratory studies revealed that this patient suffered from antibody-mediated thrombocytopenia with unusual characteristics that we have called pseudo-Bernard-Soulier syndrome.     

The Effect of Prednisone on Platelet Function Tests

Ivy bleeding time, capillary fragility, threshold ADP concentration for secondary platelet aggregation and platelet adhesiveness were found to be unchanged by 2 d and 6 weeks of treatment with prednisone in 22 consecutive patients with collagen or haematological diseases. Initial high platelet counts were unchanged after 2 d of treatment, but fell significantly to normal values after 6 weeks of treatment. Initial high levels of factor Vlll-related antigen increased insignificantly following 2 d of treatment, but after 6 weeks of treatment the increase was significant. It is concluded that in patients of this category a 6-week treatment with commonly used doses of prednisone does not significantly affect platelet function.     

ITP in pregnancy: Use of the bleeding time as an indicator for treatment

Summary ITP is a relatively common disorder seen in pregnancy. Current recommendations for management of patient with ITP recommend maintaining the platelet count above 50×10⁹/L and the bleeding time less than 20 min. It has been well documented that the bleeding time in ITP is disproportionately shortened in many patients relative to the platelet count. We present a prospective study of 24 ITP patients in whom the bleeding time was used as an indicator for therapeutic intervention in pregnancy. Indications for therapy with prednisone and/or intravenous gammaglobulin were the following: significant clinical hemorrhage due to thrombocytopenia; bleeding time of greater than 20 min at the baseline platelet count; for normalization of hemostasis prior to delivery or surgical procedure. Caesarean section was performed only in cases in which there were obstetrical indications for this mode of delivery or when the fetal platelet count (obtained by fetal scalp vein sample) was less than 50×10⁹/L. Of 24 patients with ITP, eight had significant thrombocytopenia (platelet count less than 50×10⁹/L) throughout pregnancy. Only two patients required prolonged prednisone therapy. Both suffered side effects of chronic prednisone administration. Four patients were treated with prednisone for a short course (10–14 days) at term to improve hemostasis for delivery. One patient was treated with intravenous gammaglobulin at term in an effort to prevent severe neonatal thrombocytopenia. Seven patients required caesarean section; the remaining 17 patients underwent vaginal delivery. Only one minor bleeding complication was seen — a small wound hematoma post caesarean section. In summary, using the bleeding time as an indiator for therapeutic inervention, treatment of ITP in pregnancy can be minimized. Thus, therapy related toxicity can be avoided.Presented at the International Workshop on ITP, August 26 and 27, 1988, Lucerne, Switzerland     

Autoimmune thrombocytopenia in sarcoidosis

Severe thrombocytopenia and splenomegaly developed in a young man with sarcoidosis. Platelet-associated immunoglobulin (IgG) was strongly positive, and platelet survival studies revealed a half-life of five and a half hours. Treatment with prednisone and vincristine led to a rise in the platelet count to 100,000/mm3 after two months with no change in the splenomegaly. Five months later, when the platelet count was normal, the level of platelet-associated IgG had fallen to normal. Repeated platelet survival studies showed an initial half-life of three hours with a second half-life of two days, associated with accumulation in the spleen. Although there was evidence for splenic sequestration of platelets, the dominant mechanism of thrombocytopenia appeared to be antibody-mediated destruction, analogous to that seen in idiopathic autoimmune thrombocytopenic purpura and responsive to immunosuppressive therapy.     

Two distinct subgroups of tirofiban-induced thrombocytopenia exist due to drug dependent antibodies that cause platelet activation and increased ischaemic events

Tirofiban-associated thrombocytopenia is due to drug-dependent antibodies (DDAbs) directed against the GPIIb/IIIa complex which can bind after drug-induced conformational changes to the receptor complex. In such cases a higher incidence of myocardial infarction and mortality has been reported raising the possibility of platelet activation. We followed consecutive cases treated with tirofiban to determine the incidence of thrombocytopenia and confirmed that this was due to tirofiban-dependent antibodies. We then tested if these antibodies could cause platelet activation in vitro and correlated this with clinical outcome. In 871 treated patients, severe thrombocytopenia was observed in 11 cases, an incidence of 1.26%. Tirofiban dependent antibodies were confirmed in all cases using a flow cytometric assay. There were two distinct presentations of thrombocytopenia, one occurring acutely, and the second a delayed thrombocytopenia occurring after several days of tirofiban exposure and in keeping with a primary immune response. The effects of DDAbs on platelet activation was analysed by measuring P-selectin (CD62p) and annexin V, in the presence or absence of tirofiban, by flow cytometry. In addition, platelet activation was sought using the serotonin release assay. In six cases there was evidence of platelet activation and this was significantly associated with further coronary ischaemic events experienced at the time of acute thrombocytopenia. Tirofiban-induced thrombocytopenia due to DDAbs is a common occurrence and can lead to platelet activation and increased thrombotic events.     

Splenectomy in Chronic Lymphocytic Leukaemia

In a retrospective study it was endeavoured to evaluate the effects of splenectomy in chronic lymphocytic leukaemia (CLL) characterised by splenomegaly. The material comprises 42 patients subjected to the operation in the course of the past 20 years. In the majority the spleen weighed more than 1000 g. The main indication for splenectomy was anaemia, while in 9 cases it was thrombocytopenia and in 14 cases hypercatabolism. Splenectomy is followed by a pronounced increase in the venous haemoglobin level and platelet count to higher values which have been recorded for up to 3 years after the procedure. In cases where data were available, there has been weight gain and a falling basal metabolic rate. Splenectomy is effective especially in cases predominated exclusively by splenomegaly, but even in cases with marked extrasplenic manifestations, splenectomy often greatly reduces the need for prednisone and cytostatics. Increasing hepatomegaly and lymphomas were not more common after splenectomy than in a control series, and the incidence of infections was not increased after the operation. For comparison, 37 non-splenectomised patients with splenomegaly were assessed. X-radiation of the spleen seems to be insufficient, since usually it has to be repeated. Splenomegaly does not decrease spontaneously and rarely after treatment with prednisone/cytostatics. The findings indicate that splenectomy of patients with CLL and increasing splenomegaly should be performed more often and presumably also earlier than recommended in the literature.     

Splenectomy in chronic lymphocytic leukaemia.

In a retrospective study it was endeavoured to evaluate the effects of splenectomy in chronic lymphocytic leukaemia (CLL) characterised by splenomegaly. The material comprises 42 patients subjected to the operation in the course of the past 20 years. In the majority the spleen weighed more than 1000 g. The main indication for splenectomy was anaemia, while in 9 cases it was thrombocytopenia and in 14 cases hypercatabolism. Splenectomy is followed by a pronounced increase in the venous haemoglobin level and platelet count to higher values which have been recorded for up to 3 years after the procedure. In cases where data were available, there has been weight gain and a falling basal metabolic rate. Splenectomy is effective especially in cases predominated exclusively by splenomegaly, but even in cases with marked extrasplenic manifestations, splenectomy often greatly reduces the need for prednisone and cytostatics. Increasing hepatomegaly and lymphomas were not more common after splenectomy than in a control series, and the incidence of infections was not increased after the operation. For comparison, 37 non-splenectomised patients with splenomegaly were assessed. X-radiation of the spleen seems to be insufficient, since usually it has to be repeated. Splenomegaly does not decrease spontaneously and rarely after treatment with prednisone/cytostatics. The findings indicate that splenectomy of patients with CLL and increasing splenomegaly should be performed more often and presumably also earlier than recommended in the literature.     

Reticuloendothelial system Fc-receptor function in patients with immune thrombocytopenia after treatment with high dose intravenous immunoglobulin

Reticuloendothelial system Fc-receptor (FcR) function was measured in 4 healthy controls and 9 patients with immune thrombocytopenia before and after therapy with high dose i.v. gammaglobulin (HDIg). Idiopathic thrombocytopenic purpura (ITP) was diagnosed in 5 patients. 2 patients with hemophilia A, 1 with acute tuberculosis and 1 with psoriasis vulgaris had thrombocytopenia that clinically resembled ITP. 4 out of 9 patients received prednisone prior to or during the study. FcR blockade was observed only in patients with ITP not receiving prednisone. In all other patients, HDIg did not induce a measurable FcR blockade. However, all except 1 patient (with acute tuberculosis) showed a marked rise in platelet counts for 2 to 12 wk. This is consistent with therapeutic efficacy of HDIg in various clinical settings of immune thrombocytopenia. All platelets were fully hemostatic and clinically no difference could be observed. This indicates that the effect of HDIg cannot be due to FcR blockade alone.     

Intermittent cyclophosphamide for the treatment of autoimmune thrombocytopenia in systemic lupus erythematosus

STUDY OBJECTIVE: To determine the effect of monthly intravenous cyclophosphamide therapy in patients with systemic lupus erythematosus and autoimmune thrombocytopenia. DESIGN: Uncontrolled, retrospective clinical study. SETTING: Government referral-based research hospital. PATIENTS: Seven patients with systemic lupus erythematosus and 2 or more months of thrombocytopenia refractory to or requiring excessive doses of corticosteroids. Two patients had also failed to respond to splenectomy and repeated intravenous methylprednisolone infusions. Six patients had severe active renal disease at the time of treatment. INTERVENTIONS: Cyclophosphamide, 0.75 to 1.0 g/m2 body surface area, was given intravenously every month for at least 4 months. Prednisone dose ranged between 0.5 to 1.0 mg/kg.d. MEASUREMENTS AND MAIN RESULTS: All seven patients had normal platelet counts within 2 to 18 weeks after cyclophosphamide treatment (one to four doses). Prednisone was tapered to 0.25 mg/kg on alternate days in all patients. All six patients had significant improvement in their renal disease and lupus serologies. Cyclophosphamide was discontinued after four to six doses in five patients. Four patients maintained normal platelet counts on low dose, alternate-day prednisone for a mean of 5.6 years of follow-up. Two patients had recurrence of thrombocytopenia 1 to 3 years after discontinuing cyclophosphamide. CONCLUSIONS: Monthly intravenous cyclophosphamide is potentially useful for the management of autoimmune thrombocytopenia in patients with systemic lupus erythematosus who are refractory to or dependent on unacceptably high doses of corticosteroids, or are experiencing side effects of conventional medical or surgical treatment.     

Severe thrombocytopenia in an acquired immunodeficiency syndrome patient associated with pentamidine-dependent antibodies specific for glycoprotein IIb/IIIa

Severe thrombocytopenia developed in a patient with acquired immunodeficiency syndrome during treatment with intravenous pentamidine for Pneumocystis carinii pneumonia. The patient's bone marrow contained adequate numbers of megakaryocytes, suggesting peripheral platelet destruction. Platelet counts ranged between less than 3 and 20 x 10(9)/L for 2 weeks despite cessation of pentamidine, platelet transfusions, high-dose intravenous IgG, and 2 mg/kg/d prednisone. Thereafter, the platelet count increased to prepentamidine levels (95 x 10(9)/L0, permitting rapid withdrawal of steroids. Testing by immunofluorescence disclosed a high-titer, pentamidine-dependent IgG antibody in the patient's acute-phase serum that almost entirely disappeared by the time the patient's platelet count returned to baseline levels. This antibody reacted only with platelet glycoprotein (GP) IIb/IIIa as shown by antigen-capture enzyme-linked immunosorbent assay using monoclonal antibodies specific for various GPs, and was absorbable by normal, but not by GPIIb/IIIa-deficient platelets (from a patient with Glanzmann's thrombasthenia). The pentamidine-dependent antibody could not be demonstrated by immunoprecipitation using the patient's serum and 125I-labeled normal platelets, although a separate pentamidine-independent antibody was detected by this method. This latter antibody reacted with two GPs having molecular weights consistent with GPIIb/IIIa, and was present in postrecovery as well as acute-phase sera. However, only the pentamidine-dependent antibody was temporally associated with the severe thrombocytopenia. Therefore, we believe that these studies demonstrate, for the first time, that intravenous pentamidine therapy can provoke formation of drug-dependent antibodies that induce immunologic thrombocytopenia.     

Intravenous gammaglobulin treatment for immune thrombocytopenia associated with infectious mononucleosis

Severe thrombocytopenia is an uncommon (incidence less than 1%) but serious complication of infectious mononucleosis. Corticosteroids have been used for therapy with variable responses reported. Five consecutive patients with infectious mononucleosis-related severe thrombocytopenia were treated with intravenous gammaglobulin (IVIG) at a dose of 400 mg/kg/day for 2-5 days. All patients appear to have had an immunologic or consumptive etiology for their thrombocytopenia as determined by increased marrow megakaryocytes. All patients were initially treated with oral prednisone 1 mg/kg/day. Due to the relatively slow response to prednisone (platelet count less than 20,000/microliters on the 8th to 13th hospital day) or increased bleeding symptoms, IVIG was initiated. Four of the five patients rapidly developed significant increases in their platelet counts (range 44,000/microliters to 97,000/microliters). Two of these responses were sustained and two relapses occurred (while on continued steroid therapy) which again responded to booster doses of IVIG at similar doses. IVIG has been previously shown to be effective in treating patients with idiopathic thrombocytopenia purpura. Historically, patients with infectious mononucleosis-related severe thrombocytopenia often are refractory to corticosteroid therapy and our limited experience suggests that IVIG may also be effective in infectious mononucleosis-related severe thrombocytopenia.     

Management of patients with chronic, refractory idiopathic thrombocytopenic purpura

Chronic refractory idiopathic thrombocytopenic purpura (ITP) is defined as ITP with persistent thrombocytopenia despite conventional initial management with prednisone and splenectomy. Rare in children, It may occur in as many as one third of adults with ITP. The goal of treatment is not cure of the ITP, but only to achieve a safe platelet count, which is arbitrarily assumed to be greater than 30,000 to 50,000/microL. The risk for major bleeding seems great only when the platelet count is less than 10,000/microL. Treatment of patients with moderate thrombocytopenia and no clinically important bleeding symptoms should be avoided. There is no accepted algorithm for management of patients with chronic refractory ITP. Observation without specific treatment must be considered a cornerstone of management. Combination regimens of Immunosuppressive agents may be required for patients with severe and symptomatic thrombocytopenia. Additional supportive care measures are also important.     

Detection of platelet antibodies in idiopathic thrombopenic purpura

The authors report the results of Dixon's assay modified by Follea in 24 cases of idiopathic thrombocytopenic purpura. The level of immunoglobulin G bound to platelet membrane was increased in 91 p. 100 of patients in the acute phase of the disease. An inverse correlation was demonstrated between platelet-bound antibody levels and platelet count as well as platelet survival. In all cases of refractory idiopathic thrombocytopenic purpura, the assay was positive and the mean level was higher. When the platelet count improved after prednisone therapy or after splenectomy, the level decreased. Platelet antibody determination seems to be useful for predicting the course of the disease. Patients with normal immunoglobulin G bound to platelet might have only C3, IgM or IgA. Dixon's assay is not specific to idiopathic thrombopenic purpura, since it is positive in other types of thrombocytopenia, but immunoglobulin G bound to platelet probably represents specific antiplatelet antibodies.     

Marked thrombocytopenia after high-dose intravenous gamma globulin in a pregnant woman with idiopathic thrombocytopenic purpura]

A 35-year-old pregnant woman had thrombocytopenia with a platelet count of 6.3 x 10(4)/microliter. After her third normal delivery, peripheral blood studies revealed that the patient had a normal Hb concentration and leukocyte count, with mild thrombocytopenia. A diagnosis of idiopathic thrombocytopenic purpura (ITP) was made based on the high megakaryocyte count of 338/microliter and PAIgG of 40.8 ng/10(7) cells in January 1995. The patient was followed without treatment. She was 9 weeks pregnant on June 7, 1996, and desired an abortion. Her platelet count was 6.3 x 10(4)/microliter, leukocyte count 8,600/microliter, and Hb 13.7 g/dl at the time. She was given high-dose intravenous gammaglobulin (Globenin-I) at 400 mg/kg/day for 5 consecutive days. The platelet count was found to have decreased markedly, to 0.9 x 10(4)/microliter on June 11. The percentage reduction in the Hb concentration, leukocyte count, and platelet count after gammaglobulin treatment was 11.7%, 46.6%, and 85.8%, respectively. The PAIgG titer had increased to 181.2 ng/10(7) cells on June 17, but hypergammaglobulinemia was suspected. The patient was started on prednisolone on June 24, and an abortion was performed on July 29. The mechanism of thrombocytopenia after infusion of Globenin-I was unknown. We suspect that Globenin-I treated with polyethylene glycol was one of the possible causes of myelosuppression in this case.     

Acute autoimmune thrombocytopenia

Childhood acute autoimmune thrombocytopenia is defined as a bleeding disorder in otherwise healthy children caused by transient destruction of platelets. It is benign, presenting mostly with skin purpura and minor bleeds. The diagnosis requires information about previous infections or immunizations, a physical examination looking for signs or symptoms for other causes of thrombocytopenia and a complete blood count with examination of the peripheral blood smear focusing on the number and morphology of platelets. Bone marrow examination is indicated only when in doubt and should be considered if prednisone therapy is planned. A threshold platelet count dividing high- and low-risk groups in immune thrombocytopenia (ITP) is not known because of problems with platelet counting in thrombocytopenia and the lack of clinical data. Immunoglobulins or glucocorticoids increase the platelet count, probably by blockage of the phagocytic monocyte-macrophage system. However, it is unclear whether this increase influences bleeding or mortality or whether the disadvantages of these medications might outweigh their benefits.     

Thrombocytopenia associated with c7E3 Fab (abciximab)

Abciximab (c7E3 Fab) inhibits platelet aggregation and is used to prevent complications of percutaneous coronary intervention. Thrombocytopenia is an often-cited complication of abciximab. Pseudothrombocytopenia is due to ethylenediaminetetraacetate (EDTA)-activated platelet agglutination, resulting in a spuriously low platelet count. We have looked at both "true" and pseudothrombocytopenia after infusion of abciximab. Sixty-six patients receiving their first exposure to abciximab after an unstable coronary event/revascularization were eligible. All the patients received a bolus of c7E3 Fab followed by a continuous infusion. Platelets were monitored in all patients at 2, 4, 12, 24, and 48 h, and more frequently if required. The incidence of thrombocytopenia and acute severe thrombocytopenia (platelet count < or =20,000/microl) was evaluated. A peripheral blood smear was performed on all patients showing thrombocytopenia to evaluate for pseudothrombocytopenia. Seventeen (25.6%) developed thrombocytopenia and nine (13.6%) developed acute severe thrombocytopenia. However, 18 of these patients had pseudothrombocytopenia. The onset of true thrombocytopenia was at 4 h after the infusion, while pseudothrombocytopenia occurred at anytime during the first 24 h. Only two (3.03%) patients required platelet transfusions. No life-threatening hemorrhagic complications were recognized. Five of six subjects with true thrombocytopenia had positive laboratory findings of disseminated intravascular coagulation; however, none had an adverse outcome. Acute severe thrombocytopenia was noted to be a relatively benign adverse effect of abciximab. There is an increasing incidence of pseudothrombocytopenia in this subgroup of patients. It would be worthwhile examining a peripheral blood smear or collecting blood for platelet counts in a heparin-coated tube in order to exclude this phenomenon and thereby prevent inappropriate discontinuation of this drug.