Episodes Of Thrombocytopenia Research Articles

Recurrent Miscarriage Syndrome and Infertility Due to Blood Coagulation Protein/Platelet Defects: A Review and Update

Three-hundred fifty-one women were referred for thrombosis and hemostasis evaluation after suffering recurrent miscarriages. All patients were referred by a high-risk obstetrician or reproductive medicine specialist after anatomic, hormonal or chromosomal defects had been ruled out. These patients were assessed over a three year period. The mean patient age at referral was 34 years and the mean number of miscarriages was 2.9 (2-9). All patients underwent a thorough evaluation for thrombophilia and, when indicated, a hemorrhagic disorder. Of the 351 patients, 29 (8%) had no defect. Of the remaining 322 patients, 7 (2%) had a bleeding disorder: 3 with platelet dysfunction, 1 with Factor XIII deficiency, 3 with von Willebrand's and 3 with Osler-Weber-Rendu. The remainder of the patients had a thrombophilia as follows: 195 (60%) had antiphospholipid syndrome, 64 (20%) had Sticky Platelet Syndrome, 38 (12%) had MTHFR mutation, 23 (7.1%) had PAI-1 polymorphism, 12 (3.7%) had Protein S deficiency, 12 (3.7%) had Factor V Leiden, 3 (1%), had AT deficiency, 3 (1%) had Heparin-Cofactor II deficiency, 3 (1%) had TPA deficiency, and 6 (2%) had Protein C deficiency. There were a total of 364 defects found in the 312 patients harboring thrombophilia; thus, several harbored two and a few harbored three separate defects. All patients with thrombophilia were treated with preconception ASA at 81 mg/day with the immediate post-conception addition of heparin or LMW heparin (Dalteparin). Both ASA and heparin/LMW heparin were used to term. The first 120 patients were treated with unfractionated heparin at 5,000 U every 24 hours, subcutaneously and the last 192 have been treated with Dalteparin at 5,000 U/day subcutaneously. The patients with MTHFR were also treated with folate at 5 mg/day + pyridoxine at 50 mg/day. All patients were carefully monitored with CBC and platelet counts, anti-Xa levels, frequent ultrasounds and physical exams. Only 2 of the thrombophilia patients suffered another miscarriage; all others had a normal term delivery. There were no pregnancy-related thromboses, no delivery complications and no episodes of post-partum thrombosis. The only bleeding consisted of 1-4 cm bruises at injection sites. No episodes of thrombocytopenia (HIT) were noted. In our experience, thrombophilia is a common cause of recurrent miscarriage and all patients with no anatomical, hormonal or chromosomal defect should be evaluated for thrombophilia or a bleeding disorder. The success rate of normal term delivery in these 312 patients was 94% using ASA + heparin or Dalteparin. In addition, side effects of therapy were minimal.

Thrombohemorrhagic Defects and Recurrent Miscarriage Syndrome.

We have assessed 351 women referred for thrombosis & hemostasis evaluation after suffering recurrent miscariages. All patients were referred by a high-risk obstetrician or reproductive medicine specialist after anatomic, hormonal or chromosomal defects had been ruled out. These patients were assessed over a three year period. The mean patient age at referral was 34 yrs. and the mean number of miscarriages was 3.4 (2–9). All patients underwent a thorough evaluation for thrombophilia and, when indicated, a hemorrhagic disorder. Of the 351 patients, 29 (8%) had no defect. Of the remaining 322 patients, 7 (2%) had a bleeding disorder: 3 with platelet dysfunction, 1 with Factor XIII deficiency, 3 with von Willebrands and 3 with Osler-Weber-Rendu. The remainder of the patients had a thrombophilia as follows: 195 (60%) had antiphospholipid syndrome, 64 (20%) had Sticky Platelet Syndrome, 38 (12%) had MTHFR mutation, 23 (7.1%) had PAI-1 polymorphism, 12 (3.7%) had Protein S deficiency, 12 (3.7%) had Factor V Leiden, 3 (1%), had AT deficiency, 3 (1%) had Heparin-Cofactor II deficiency, 3 (1%) had TPA deficiency, and 6 (2%) had Protein C deficiency. There were a total of 364 defects found in the 312 patients harboring thrombophilia; thus, several harbored two and a few harbored three separate defects.All patients with thrombophilia were treated with preconception ASA at 81 mg. / day with the immediate post-conception addition of heparin or LMW heparin (Dalteparin). Both ASA and heparin / LMW heparin were used to term. The first 120 patients were treated with unfractionated heparin at 5,000 U every 12 hours, subcutaneously and the last 192 have been treated with Dalteparin at 5,000 U / day subcutaneously. The patients with MTHFR were also treated with folate at 5 mg. / day + pyridoxine at 50 mg. / day. All patients were carefully monitored with CBC & platelet counts, anti-Xa levels, frequent ultrasounds and physical exams. Only 2 of the thrombophilia patients suffered another miscarriage; all others had a normal term delivery. There were no pregnancy-related thromboses, no delivery complications and no episodes of post-partum thrombosis. The only bleeding consisted of 1 – 4 cm bruises at injection sites. No episodes of thrombocytopenia (HIT) were noted.In our experience, thrombophilia is a common cause of recurrent miscariage and all patients with no anatomical, hormonal or chromosomal defect should be evaluated for thrombophilia or a bleeding disorder. The success rate of normal term delivery in these 312 patients was 94% using ASA + heparin or Dalteparin. In addition, side effects of therapy were minimal.

Clinical Features, Natural History, and Treatment Outcome of Idiopathic Cyclic Thrombocytopenia: Systematic Analysis of 51 Cases Reported in the Literature.

Background: Cyclic thrombocytopenia (CTP) is an uncommon condition characterized by periodic fluctuations in platelet counts, typically resulting in episodes of thrombocytopenia alternating with normal platelet counts. Because of similar clinical presentation, CTP is mostly misdiagnosed as idiopathic thrombocytopenic purpura (ITP). The natural history and optimal therapy are not defined. Methods: The English medical literature was reviewed for reported CTP cases up to December 2003 using PubMed. Only idiopathic forms (not associated with other hematologic disorders) of CTP were included. Results: Fifty one cases of CTP were identified. There was a female predominance (33:18) with a median age at diagnosis of 35 years (range, 1–70). Serious bleeding episodes were reported in 13 patients (27%) at various time points, while 7 (15%) were asymptomatic. Twenty-six (51%) patients were given an initial diagnosis of ITP. The median time from ITP to CTP diagnosis was 24 months (range, 1–420). The median nadir and peak platelet counts were 10 x 109/L (range, 1–90) and 330 x 109/L (range, 72–2,300), respectively. Rebound thrombocytosis occurred in 18 patients (35%). Most of the patients had regular platelet cycles within 21–35 days. In the 20 patients who were premenopausal and in whom relationship between platelet counts and menstrual cycles were studied, 16 (80%) had CTP in phase with menstrual periods. Bone marrow biopsy was performed during platelet nadir in 45 patients. Megakaryocytes were normal or increased in number in 33 patients (73%) and decreased or absent in 12 patients (27%). Anti-platelet antibodies were measured in 42 patients and found to be present in 17 (40%). After a median follow-up of 31 months (range, 3–558), 2 (4%) patients had died of disease; 14 (27%) were alive without disease; 34 (67%) were alive with disease; and 1 (2%) died with disease. Ten (20%) patients did not require therapy. In 9 patients, treatment was not described. The rest of the 32 patients received various therapies appropriate for ITP (Table). Half (5/10) of those who received hormonal therapy (danazol, progestin, or estrogen/progestin) responded. Conclusions: When evaluating patients with suspected ITP, CTP should always be included in the differential diagnoses. CTP generally does not respond to standard ITP treatments, including corticosteroids, splenectomy, and intravenous immunoglobulin. Two clinical features relatively unique to CTP besides periodic thrombocytopenia are rebound thrombocytosis unrelated to recent splenectomy and platelet nadirs occurring during menstruation. When a diagnosis of CTP is made, patients must be offered a period of observation, as many may not require treatment. If treatment is clinically indicated, hormonal therapy may provide the best response. TREATMENT N CR PR RR (%) Corticosteroids 26 0 0 0 Splenectomy 19 1 1 10 Intravenous immunoglobulin 11 0 0 0 Cyclosporine 5 1 2 60 Danazol 5 3 0 60 Vincristine 5 0 0 0 Azathioprine 4 1 0 25 Plasma infusion 4 0 0 0 Estrogen/progestin 3 1 0 33 Others 21 2 1 14

Neonatal immune thrombocytopenia

Background: Neonatal immune thrombocytopenia, a consequence of transplacental transfer of antiplatelet antibodies can result in serious bleeding with disastrous consequences in the otherwise healthy newborn. Methods: Over 2 years at a service hospital, 5 mothers with chronic autoimmune thrombocytopenia and one with maternal alloimmunisation delivered, which comprised the study sample. Results: Of these, two ladies suffered episodes of thrombocytopenia in the current pregnancy. They were provided platelet transfusions and intravenous immunoglobulins. All patients delivered vaginally. Cord blood platelet was normal in all cases. Three babies developed thrombocytopenia, two due to autoimmune and one alloimmune pathology. The nadir of thrombocytopenia occurred in 36–72 hours with recovery taking place in 10 days. The clinical manifestations were petechiae, ecchymosis, gastric bleed and oozing from vitamin K injection site. Two of the affected babies were provided intravenous immunoglobulins and one steroids. Only one of the two mothers who suffered thrombocytopenia during pregnancy and was provided intravenous immunoglobulins was associated with neonatal thrombocytopenia, an inconsistent relation. It was also observed that antenatally provided immunoglobulins raised effectively maternal rather than fetal platelet counts. However, postnatal immunoglobulins were efficacious in thrombocytopenic neonates. Conclusion: Thus inspite of several therapeutic and preventive modalities being described, the optimum management strategy of immune mediated perinatal thrombocytopenia is yet in evolution.

Is the fall in platelet count associated with intensive care unit acquired pneumonia?

Intensive Care Unit Acquired Pneumonia is the most frequent infection among patients receiving mechanical ventilation and has an important impact on patient mortality. Thrombocytopenia is one of the most common laboratory abnormalities in Intensive Care Unit (ICU). The aim of this study was to evaluate the relationship between platelet count and Intensive Care Unit Acquired Pneumonia (ICUAP). Medical records of 41 mechanically-ventilated pulmonary ICU patients having at least one ICUAP were reviewed. The date of first ICUAP, etiologic pathogens, platelet count at admission, the nadir value within seven days before and after the date of ICUAP, development of thrombocytopenia (platelet <100 x 10(3)/mm(3)), acute physiology and chronic health evaluation (APACHE) II scores on admission, medications and events that can effect platelet count and other laboratory values were noted. The meantime for the first ICUAP was 13 +/- 10.3 days after ICU admission. The nadir platelet count associated with ICUAP (ICUAPplatelet count) was seen on 12.1 +/- 11.3th day after ICU admission; with a significant fall (30% fall) when compared to admission platelet count (platelet counts are 157.2 +/- 87.4 x 10(3)/mm(3), 224.1 +/- 106.3 x 10(3)/mm(3) respectively, p <0.001). Fifteen of the 41 patients had an episode of thrombocytopenia during their ICU stay and these patients had a higher mortality rate than nonthrombocytopenics (mortality rates are 80% and 50% respectively, p = 0.05). Besides the proven role of thrombocytopenia in prognosis in ICU, the significant fall in platelet count can be an early warning parameter and possible diagnostic hint for severe infections in ICU such as ICUAP.

Is the fall in platelet count associated with intensive care unit acquired pneumonia?

Intensive Care Unit Acquired Pneumonia is the most frequent infection among patients receiving mechanical ventilation and has an important impact on patient mortality. Thrombocytopenia is one of the most common laboratory abnormalities in Intensive Care Unit (ICU). The aim of this study was to evaluate the relationship between platelet count and Intensive Care Unit Acquired Pneumonia (ICUAP). Medical records of 41 mechanically-ventilated pulmonary ICU patients having at least one ICUAP were reviewed. The date of first ICUAP, etiologic pathogens, platelet count at admission, the nadir value within seven days before and after the date of ICUAP, development of thrombocytopenia (platelet <100 x 10(3)/mm(3)), acute physiology and chronic health evaluation (APACHE) II scores on admission, medications and events that can effect platelet count and other laboratory values were noted. The meantime for the first ICUAP was 13 +/- 10.3 days after ICU admission. The nadir platelet count associated with ICUAP (ICUAPplatelet count) was seen on 12.1 +/- 11.3th day after ICU admission; with a significant fall (30% fall) when compared to admission platelet count (platelet counts are 157.2 +/- 87.4 x 10(3)/mm(3), 224.1 +/- 106.3 x 10(3)/mm(3) respectively, p <0.001). Fifteen of the 41 patients had an episode of thrombocytopenia during their ICU stay and these patients had a higher mortality rate than nonthrombocytopenics (mortality rates are 80% and 50% respectively, p = 0.05). Besides the proven role of thrombocytopenia in prognosis in ICU, the significant fall in platelet count can be an early warning parameter and possible diagnostic hint for severe infections in ICU such as ICUAP.

Idiopathic cyclic thrombocytopenia

Cyclic thrombocytopenia (CTP) is an uncommon disorder characterized by periodic fluctuations in platelet counts, typically resulting in episodes of thrombocytopenia alternating with normal platelet counts. While some CTP cases are associated with a primary hematologic disease, most are idiopathic. Patients with CTP are frequently misdiagnosed as idiopathic thrombocytopenic purpura (ITP) because CTP has clinical features very similar to ITP. When evaluating patients with suspected ITP, CTP should always be included in the differential diagnoses because CTP generally does not respond to standard ITP treatments, including corticosteroids, splenectomy, and intravenous immunoglobulin. Two clinical features relatively unique to CTP besides periodic thrombocytopenia are rebound thrombocytosis unrelated to recent splenectomy and platelet nadirs occurring during menses. When a diagnosis of CTP is made, patients must be offered a period of observation, as many may not require treatment. If treatment is clinically indicated, the literature suggests that hormonal therapy provides the best response.

Biphasic rattlesnake venom-induced thrombocytopenia

Thrombocytopenia is a common occurrence in moderate to severe crotaline envenomation. The exact mechanism by which rattlesnake venom leads to thrombocytopenia is unclear, but aggressive treatment with crotaline-specific antivenom often leads to resolution of this disorder. Crotalinae Polyvalent Immune Fab (CroFab TM, Protherics Inc., Nashville, TN) (crotaline Fab) is now available for the treatment of symptomatic rattlesnake envenomation. Although recurrence of thrombocytopenia has been reported in patients after envenomation treated with crotaline Fab, cases refractory to this therapy have not been described. We report a case of severe crotaline envenomation that appears to have exhibited two separate episodes of thrombocytopenia, only one of which responded to antivenom. The second, later phase was refractory to both crotaline Fab as well as traditional Antivenin (Crotalinae) Polyvalent (Wyeth-Ayerst Pharmaceuticals, Philadelphia, PA) (ACP). By reviewing the literature regarding venom-induced thrombocytopenia, we attempt to explain this “biphasic” phenomenon and the inability of crotaline Fab to reverse this toxic effect.

Single-center experience with mycophenolate mofetil in pediatric renal transplant recipients.

Mycophenolate mofetil (MMF), a potent and specific inhibitor of guanosine nucleotide synthesis, is a new immunosuppressive drug used to prevent rejection in transplant patients. Extensive data on its utility and efficacy exists in adult patients but there is limited experience in pediatrics. Twenty-four children (14 male, 10 female; 2-19 yr of age), eight of whom had received living-related donor (LRD) transplants and 16 of whom had received cadaveric donor (CD) transplants, have been treated with MMF in our institution since September 1996. MMF was administered for a duration ranging from 13 weeks to 38 months, at an average dose of 600 mg/m2 (range: 200-1,000 mg/dose) every 12 h, for a total experience of 304 patient months. MMF capsules were used in 16 patients and/or pediatric suspension in eight. Five patients were switched to MMF from azathioprine as a result of rejection episodes or inability to taper prednisone, between 5 weeks and 3.5 yr post-transplant. All patients received prednisone, cyclosporin A (CsA), and induction therapy with anti-lymphocyte globulin (19 patients), anti-thymocyte globulin (one patient) or daclizumab (four patients). In 12 patients started on MMF at the time of CD transplant, five (42%) had an acute rejection episode. In seven who received a LRD transplant, one (14%) had an acute rejection episode. No patients who were converted to MMF were treated for acute rejection following conversion to MMF. One LRD graft was lost at 19 days following injury to the donor artery at the time of retrieval. At the last follow-up, the average creatinine level was 93 micromol/L and average urea level was 8.6 mmol/L. One patient developed epigastric distress. Three patients developed diarrhea/abdominal pain requiring dose adjustment. Five episodes of leukopenia and one episode of thrombocytopenia required dose adjustment. Two patients developed symptomatic cytomegalovirus (CMV) infection, one while on acyclovir prophylaxis. No malignancy has been encountered to date. Hence, MMF can be administered safely to children with good effect and with an acceptable side-effect profile.

Administration of abciximab to patients receiving tirofiban or eptifibatide: effect on platelet function

OBJECTIVESThe goal of this study was to evaluate platelet function and to preliminarily assess the clinical safety of sequential treatment with tirofiban or eptifibatide followed by abciximab in patients undergoing percutaneous coronary intervention (PCI).BACKGROUNDAn increasing number of acute coronary syndrome (ACS) patients are treated early with tirofiban or eptifibatide. Some later require PCI and may benefit from switching to abciximab, for which long-term benefits have been reported.METHODSFifty ACS patients planned for PCI were enrolled. Twenty-five patients received tirofiban followed by abciximab. Ten patients received eptifibatide followed by abciximab. Fifteen patients received only abciximab. All patients had blood samples drawn six times during the therapeutic course. Platelet function was evaluated by ADP- and TRAP-induced aggregation, flow cytometry analysis of fibrinogen binding and the cone and plate(let) analyzer, which tests shear rate-dependent platelet activation.RESULTSAdministered after tirofiban, abciximab caused a significant further decline in platelet function, as evidenced by all methods. Administered after eptifibatide, abciximab caused a significant further reduction in platelet function, as assessed by the cone and plate(let) analyzer and fibrinogen binding methods. The platelet inhibition achieved by the combination therapy was always greater than or equal to that achieved by abciximab alone. There were no major bleeding or severe thrombocytopenia episodes. Three of the 35 combination therapy patients and one of the 15 who received abciximab alone had minor bleeding.CONCLUSIONSThis is the first in vivo study of combination intravenous platelet glycoprotein IIb/IIIa inhibitor therapy. Administration of abciximab immediately after tirofiban or eptifibatide therapy effectively inhibits platelet function and appears to be safe.

Occurrence of Thrombocytopenia in Psychiatric Patients Taking Valproate

Few studies, with conflicting results, have examined the occurrence of thrombocytopenia with valproate administration. This study assessed whether the platelet-lowering effects of valproate are increased among elderly psychiatric patients. The charts of 39 psychiatric inpatients taking valproate were reviewed. Information on hematologic function and on doses and serum levels of valproate at sequential intervals over a 12-month period was abstracted. Data for subjects age <60 years (nonelderly subjects) and those age >/=60 years (elderly subjects) were compared. More than half (53.8%) of the elderly patients but only 13.0% of the nonelderly patients had at least one episode of thrombocytopenia. This difference corresponded to a significantly greater lowering of platelet counts among elderly patients than among nonelderly patients. The high rate of thrombocytopenia in our study suggests the need for routine monitoring of platelet counts among patients taking valproate, particularly among elderly patients.

Bipolar affective disorder and thrombocytopenia

AbstractThis report describes the case of a 62 year old man with late onset bipolar affective disorder whose mood swings were associated with episodes of thrombocytopenia. The inter-relationships between affective symptoms, the immune system and the hypothalamic pituitary axis are discussed.

Conservative Management of Chemotherapeutic-Induced Thrombocytopenia in Women with Gynecologic Cancers

During the course of four recent dose-intense chemotherapy trials, the routine practice of transfusing patients with platelet counts < 20,000/microliters was changed to a more conservative style of management limiting prophylactic transfusions to patients with platelet counts < 5000/microliters. One hundred seventy-nine episodes of thrombocytopenia in 46 patients enrolled in four dose-intense chemotherapy trials were evaluated. Thirty-two patients had advanced carcinoma of the ovary, 10 had pelvic sarcomas, and 4 had cervical cancer. Of the 179 episodes of thrombocytopenia evaluated, 100 exhibited severe thrombocytopenia (platelet count < 20,000/microliters). Of these 100 episodes, 30 received prophylactic platelet transfusions while 70 did not. Thirty-eight episodes of thrombocytopenia were 5000-10,000/microliters, 24 of which received prophylactic platelet transfusions while 14 did not. Eighteen episodes (10%) of thrombocytopenia resulted in minor bleeding and all occurred during severe thrombocytopenia. Minor bleeding occurred in 27% of episodes of severe thrombocytopenia receiving prophylactic platelet transfusions versus 14% not transfused (P = 0.2). Of the 38 episodes of thrombocytopenia 5000-10,000/microliters, minor bleeding occurred in 17% receiving prophylactic platelet transfusions versus 24% not transfused (P = 0.95). None of the 179 episodes of thrombocytopenia resulted in major bleeding, including 70 episodes of thrombocytopenia < 20,000/microliters not receiving prophylactic platelet transfusions which included 14 episodes of thrombocytopenia between 5000-10,000/microliters. In conclusion, in women with gynecologic cancer and chemotherapy-induced thrombocytopenia, we safely limited prophylactic platelet transfusions for episodes of thrombocytopenia < 5000/microliters. We hope our study will prompt prospective, randomized trials evaluating the need of prophylactic platelet transfusions for chemotherapy-induced thrombocytopenia in patients with solid tumors.

Thrombopoietin from human embryonic kidney cells causes increased thrombocytopoiesis and decreased erythropoiesis in mice

Recent studies have shown that large doses of erythropoietin (EPO) administered daily over a 7-day period elevate erythropoiesis and lead to marked thrombocytopenia. Conversely, anaemia was found in mice following stimulation of thrombocytopoiesis by an acute thrombocytopenic episode. Although erythropoiesis and thrombocytopoiesis have been studied in mice after treatment with either hypoxia or EPO injection, only the effects of endogenous thrombopoietin (released after an acute episode of thrombocytopenia caused by an injection of antiplatelet serum) on erythropoiesis have been investigated. Therefore, we injected mice with a potent source of thrombopoietin and evaluated both thrombocytopoiesis and erythropoiesis at 3 and 5 days after treatment. The data show that thrombopoietin elevated thrombocytopoiesis with a concomitant reduction in erythropoiesis. We found significantly elevated percentage 35S incorporation into platelets, platelet sizes, and total circulating platelet masses following thrombopoietin injections at both 3 and 5 days; haematocrits, reticulocyte counts, and total circulating red blood cell masses were reduced significantly in these same mice. Compared to controls treated with human serum albumin, megakaryocyte size was increased on day 3, and megakaryocyte numbers were elevated on day 5 in mice treated with thrombopoietin. Thrombopoietin did not change the blood volume of mice, but did cause an increase in splenic weight. However, splenic sequestration of red blood cells was not the cause of anaemia in mice treated with thrombopoietin, since splenectomised mice also showed increased thrombocytopoiesis with decreased erythropoiesis. These data agree with previous studies showing an inverse relation between erythropoiesis and thrombocytopoiesis, and are consistent with the hypothesis that the erythrocytic and megakaryocytic cell lines are in competition.

Acquired cyclic thrombocytopenia‐thrombocytosis with periodic defect of platelet function

A periodic fall of platelet number characterizes an acquired pathological condition named cyclic thrombocytopenia. We observed a patient in whom the episodes of thrombocytopenia (platelet number less than 50 x 10(9)/l) were followed regularly by thrombocytosis (700-2300 x 10(9) platelets/l). The period of platelet count fluctuation was about 40 d. Morphological examination of bone marrow showed the cyclic disappearance of mature and immature megakaryocytes; bone marrow cultures revealed a periodic severe defect of both multilineage and single-lineage progenitor cell growth. When platelet count was falling, a mild defect of platelet aggregation and ATP release was observed, while platelet function was normal when platelet count was rising. Prednisone, thymopentin, high-dose intravenous gamma-globulin and splenectomy were without effect. After 4 years of cyclic platelet and megakaryocyte fluctuations, stable amegakaryocytic thrombocytopenia developed and the patient died of haemorrhagic stroke.

Recurrent episodes of thrombocytopenia during treatment with sodium stibogluconate

Recurrent episodes of thrombocytopenia during treatment with sodium stibogluconate

Therapy of Immune Mediated Thrombocytopenia

Fifteen dogs with immune mediated thrombocytopenia (IMT) were studied retrospectively. All dogs had a thrombocyte count below 50,000/μl when response to therapy was studied. Platelet counts greater than 50,000/μl were present in all dogsl within 2–9 days of initiating medical therapy. Eight dogs experienced a single episode of thrombocytopenia and seven dogs relapsed over the following 5 to 24 months. Clinical parameters from dogs that experienced a single episode of IMT were compared with data from dogs that relapsed to determine whether any information would identify dogs that were prone to relapse. Signalment, severity of thrombocytopenia, and time to achieve a platelet count above 50,000/μl were found not to differ (P &gt; 0.05) between these two groups.Five of the seven dogs with relapsing IMT were splenectomized after 2 to 4 episodes (mean, 2.8 ± 0.8) of thrombocytopenia over 2 to 14 months. The postoperative progress of these five dogs was followed for 6 to 17 months. Platelet counts were sustained above 200,000/μ1 in 4/5 after splenectomy and it was possible to discontinue medical therapy in these dogs. In comparison, the 2 relapsing IMT cases that were not splenectomized continued to require intermittent immunosuppressive therapy.We conclude that signalment and routine pretreatment laboratory test results are not useful in distinguishing dogs with relapsing IMT from those that will experience one episode of IMT. Seemingly, splenectomy is useful in the management of dogs with relapsing IMT. (Journal of Veterinary Internal Medicine 1990; 4:4–7)

Correlation of a quinidine-induced platelet-specific antibody with development of thrombocytopenia

The rapidity by which drug-dependent antiplatelet antibodies can develop is not known, since patients are only studied during or after the episode of thrombocytopenia. This report describes the development of quinidine-induced immune thrombocytopenia in a healthy volunteer during a drug study. The thrombocytopenia developed within two weeks of initiation of quinidine therapy. During the thrombocytopenic episode, but not before receiving the drug, the patient had an IgG antiplatelet antibody that bound to control platelets in the absence of the drug. This antibody was absent when the drug was discontinued and the platelet count rose. The patient's acute serum also induced the release of serotonin from control platelets, and the reaction was enhanced by quinidine. This indicates that drug-dependent antiplatelet antibodies can develop rapidly and supports the hypothesis that quinidine-induced thrombocytopenia is due to a quinidine-dependent platelet-specific IgG.

Abnormal VIII: von Willebrand Factor Patterns in the Plasma of Patients With the Hemolytic-Uremic Syndrome

Plasma VIII:von Willebrand factor antigen (VIII:vWF) levels were elevated approximately two- to eightfold in seven patients (three adults and four children) during acute episodes of thrombocytopenia, renal failure, and hemolytic anemia (the hemolytic-uremic syndrome, HUS). In all seven patients, there was an alteration in plasma VIII:vWF patterns during these acute HUS episodes, so that the largest VIII:vWF forms were relatively decreased. Plasma VIII:vWF multimer patterns returned to normal, or nearly to normal, as platelet counts returned to preexisting levels, even in the patients whose recovery of renal function was incomplete and whose plasma VIII:vWF antigen level remained above normal. The sister of one of the HUS patients had a similar clinical prodrome (gastroenteritis) that was not followed by thrombocytopenia or renal failure and was not accompanied by an elevated level or abnormal forms of plasma VIII:vWF. These results suggest that an alteration in VIII:vWF metabolism, distribution, or interaction with platelets is associated with acute HUS episodes. In contrast to patients with chronic relapsing thrombotic thrombocytopenic purpura, none of the HUS patients (either during or after the acute HUS episodes) had a defect in the conversion of unusually large VIII:vWF multimers derived from endothelial cells to the VIII:vWF forms found in normal plasma.

Abnormal VIII: von Willebrand factor patterns in the plasma of patients with the hemolytic-uremic syndrome

Plasma VIII:von Willebrand factor antigen (VIII:vWF) levels were elevated approximately two- to eightfold in seven patients (three adults and four children) during acute episodes of thrombocytopenia, renal failure, and hemolytic anemia (the hemolytic-uremic syndrome, HUS). In all seven patients, there was an alteration in plasma VIII:vWF patterns during these acute HUS episodes, so that the largest VIII:vWF forms were relatively decreased. Plasma VIII:vWF multimer patterns returned to normal, or nearly to normal, as platelet counts returned to preexisting levels, even in the patients whose recovery of renal function was incomplete and whose plasma VIII:vWF antigen level remained above normal. The sister of one of the HUS patients had a similar clinical prodrome (gastroenteritis) that was not followed by thrombocytopenia or renal failure and was not accompanied by an elevated level or abnormal forms of plasma VIII:vWF. These results suggest that an alteration in VIII:vWF metabolism, distribution, or interaction with platelets is associated with acute HUS episodes. In contrast to patients with chronic relapsing thrombotic thrombocytopenic purpura, none of the HUS patients (either during or after the acute HUS episodes) had a defect in the conversion of unusually large VIII:vWF multimers derived from endothelial cells to the VIII:vWF forms found in normal plasma.