Thrombocytopenic purpura as a manifestation of pulmonary tuberculosis is very rare. We report a case of 25-year-old female who presented with thrombocytopenia-induced purpuric spots and an abnormal chest X-ray. There was no hepatosplenomegaly while the bone marrow examination revealed normal maturation of myeloid and erythroid series with increased megakaryocytes. Acid fast bacilli were seen in the sputum microscopy. A diagnosis of sputum smear positive pulmonary tuberculosis along with immune thrombocytopenia was made. High dose intravenous immunoglobulin therapy along with antituberculous drugs corrected the thrombocytopenia and also cured pulmonary tuberculosis. This case report illustrates the causal association between immune thrombocytopenia and tuberculosis.
Immune thrombocytopenia; Pulmonary tuberculosis; Purpura
We report a case of concurrent thrombotic thrombocytopenic purpura (TTP) and immune thrombocytopenic purpura (ITP) in a 63-year-old woman who had been receiving treatment with bevacizumab for metastatic neuroendocrine tumour (NET). At diagnosis, she had severe anaemia and thrombocytopenia with elevated lactate dehydrogenase and many schistocytes on the peripheral blood smear. She was treated with frequent fresh frozen plasma infusions and plasmapheresis with poor response. Later, she was found to have platelet surface glycoprotein antibodies in the serum and received four cycles of rituximab, vincristine, cyclophosphamide (rituximab-CVP) and steroids in addition to plasma therapy. The haemoglobin and platelet counts improved. To our knowledge, this is the first reported case of concurrent TTP and ITP in a patient with metastatic NET diagnosed while receiving bevacizumab therapy, who was successfully treated with the combination of rituximab, vincristine, cyclophosphamide and steroids.
Tuberculosis has a variety of hematological manifestations. Immune thrombocytopenic purpura is an uncommon manifestation of tuberculosis. We present a case of disseminated tuberculosis with isolated thrombocytopenia. While TB granulomas in the bone marrow can themselves cause hematological abnormalities, persistent thrombocytopenia refractory to anti-TB therapy may be ITP associated with TB.
Disseminated tuberculosis; immune thrombocytopenic purpura; intravenous immunoglobulin
The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, we studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. We observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP (less than 10%), (P less than 0.01). We obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3 (P less than 0.01, r = 0.53). We demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. The isolated IgM fraction from these two plasmas was able to activate complement and place 3H-C3 on normal platelets. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.
Although various hematologic abnormalities are seen in tuberculosis, immune thrombocytopenic purpura is a rare event.
We report a case of a 29 year-old male who was presented with immune thrombocytopenia-induced hemoptysis, macroscopic hematuria and generalized petechiae. The patient was found to have clinical, microbiological and radiological evidence of active pulmonary tuberculosis. The immune thrombocytopenic purpura was successfully treated with anti-tuberculous drugs combined with corticosteroids and high dose immune globulin therapy.
Immune thrombocytopenic purpura can be one of the hematological manifestations of tuberculosis which has a global prevalence with increasing incidence secondary to HIV infection.
Tuberculosis; immune thrombocytopenic purpura; immune thrombocytopenia
Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications.
immune thrombocytopenic purpura; pediatrics; recombinant factor VIIa; FX, factor X; HPF, high-power field; ITP, immune thrombocytopenic purpura; IVIG, intravenous immunoglobulin G; rFVIIa, recombinant factor VIIa
Two adult cases of thrombohaemolytic thrombocytopenic purpura are described. Both showed striking morphological changes in the red cells with increased saline osmotic fragility, in addition to thrombocytopenia and generalized hyaline thrombi affecting small blood vessels. These changes support the hypothesis that this is a triple auto-immune disorder affecting red cells, platelets, and small blood vessels.
Three cases of immune thrombocytopenic purpura after the first
dose of recombinant hepatitis B vaccine occurred in infants under 6 months of age. Other possible causes of this condition were excluded.
Antiplatelet antibodies were present. A defect in platelet production
was excluded in two children. Corticosteroid treatment was effective.
Subsequent administration of other vaccines (against polio, diphtheria,
and tetanus) did not cause relapse of thrombocytopenia.
Six patients had serious complications as consequences of treatment of idiopathic thrombocytopenic purpura. Five had splenectomy-related complications, one of them developed fatal intra-abdominal bleeding. Three patients acquired operation-related serious infection, two of them died. Serious neutropenia after vinblastine-loaded platelets occurred in one patient leading to pseudomonas septicaemia and panophthalmitis with permanent vision loss of left eye. Recurrence thrombocytopenia occurred in every case during serious complications. Early detection by awareness of the possibility of serious complications can reduce morbidity and mortality occurring after therapy of idiopathic thrombocytopenic purpura.
A case study involving a 55-year-old Caucasian male with end-stage glomerulosclerosis is presented here. Kidney biopsies showed no deposits on imunofluorescent microscopy. Relapsing massive haemoptysis and suspected bronchovascular malformation required lung lobectomy which revealed malformative and tortuous small blood vessels, with no vasculitis. Blood antinuclear antibodies, antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were undetectable. Seric immunoglobulins and complement levels were normal. Three months later, arthralgia and joint oedema first appeared. Skin biopsy revealed vasculitis immune-reactive to immunoglobulin A. Systemic corticotherapy was then started. Two weeks later, the patient presented with abdominal pain melena and rectal bleeding (haematoquesia). Endoscopic study showed diffuse gastrointestinal haemorrhage. Angiographic study revealed diffuse lesions compatible with vasculitis and haemorrhage from multiple spots. Cyclophosphamide and then intravenous immunoglobulin were associated to treatment without response. Increasing blood loss occurred, with massive gastrointestinal haemorrhage and haemorrhagic ascitis. Death occurred due to uncontrolled diffuse bleeding. Necropsy findings showed generalised small vessels vasculitis compatible with Henoch–Schönlein purpura.
Background and Objectives:
Laparoscopic surgical techniques in pregnancy have been accepted and pose minimal risks to the patient and fetus. We present the first reported case of a pregnant woman with immune thrombocytopenia purpura who underwent laparoscopic splenectomy during the second trimester.
Methods and Results:
The anesthesia, hematology, and obstetrics services closely followed the patient's preoperative and intraoperative courses. After receiving immunization, stress dose steroids, and prophylactic antibiotics, she underwent a successful laparoscopic splenectomy. After a short hospital stay, the patient was discharged home.
Immune thrombocytopenia purpura can be an indication for splenectomy. As demonstrated in appendectomy, cholecystectomy, and our case presentation, laparoscopic splenectomy can be safely performed during pregnancy.
Thrombocytopenia; Laparoscopy; Splenectomy; Pregnancy
A 36 yr-old man of Israeli descent with a history of childhood splenectomy for severe thrombocytopenia and a family history of autoimmune lymphoproliferative syndrome (ALPS), presented with severe immune thrombocytopenic purpura refractory to standard therapy. He was found to possess a heterozygous mutation in the Fas gene (also termed TNFRSF6, CD95, Apo-1) affecting the donor splice site of intron 7 (IVS7+2 T>C). This frameshift mutation truncates the cytoplasmic domain of the Fas death receptor, resulting in circulating CD4/8 double negative T lymphocytes, lymphadenopathy and autoimmune complications typical of ALPS. Administration of Rituximab in this patient was associated with a durable hematologic response (currently more than 12 months). This report highlights the need to consider rare inherited causes of thrombocytopenia in adults with a family history of immune cytopenia(s) and the effective use of anti-CD20 monoclonal antibody in patients unresponsive to immunosuppression and splenectomy.
Rituximab; immune thrombocytopenic purpura; autoimmune lymphoproliferative syndrome; TNFRSF6; Fas
Thrombotic thrombocytopenic purpura (TTP) is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD) is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.
Sunitinib (Sutent: Pfizer, New York, NY, U.S.A.) is an oral multi-targeted tyrosine kinase inhibitor approved for use in various solid tumour malignancies. Many side effects secondary to sunitinib have been documented. In particular, sunitinib administration is known to result in thrombocytopenia, with the cause being attributed to myelosuppression. Here, we present the first case report to demonstrate immune-mediated thrombocytopenia secondary to sunitinib administration.
Breast cancer; thrombocytopenia; sunitinib
Thrombotic Thrombocytopenic Purpura (TTP) is a life threatening, multisystem disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological changes, renal failure, and fever. These signs and symptoms are thought to be caused by microthrombi, composed of agglutinated platelets and fibrin, which deposit in the arterioles and capillaries without mediation by an inflammatory process. TTP can occur in the first two weeks of initiation of Clopidogrel therapy. Early signs of TTP may be a skin reaction, which may precede the onset of TTP or it may be other type of purpura or neurological changes. We report the clinical and laboratory findings in a 67 years old female patient in whom TTP developed soon after treatment with 40 mg/day oral Clopidogrel after 8 days. She developed thrombocytopenia (platelets count 12000 /mm3). Her clinical signs and symptoms were fever (39.6C), bleeding from the nose and gum, large skin bruises (purpura and ecchymoses), neurological changes including hallucinations, bizarre behavior, altered mental status (fluctuating), headache, and renal dysfunction. Physicians should be aware of the possibility early onset of this syndrome when initiate Clopidogrel treatment.
Thrombotic Thrombocytopenic Purpura (TTP); Clopidogrel; plasma exchange
Thrombotic thrombocytopenic purpura (TTP) is an uncommon life-threatening disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, commonly associated with infections, malignancy, drugs, and autoimmune diseases. We report a case of 19-year-old previously healthy female that presents with anemia and thrombocytopenia diagnosed with thrombotic thrombocytopenic purpura that was treated successfully with plasmapheresis and corticosteroids. Laboratory findings also revealed antinuclear antibodies and antibodies to double-stranded DNA. Two weeks after presentation developed inflammatory arthritis, fulfilling diagnostic criteria for systemic lupus erythematosus (SLE). Prompt diagnosis and treatment with plasma exchange and corticosteroids should be instituted as soon as the diagnosis of TTP is suspected, even if other diagnoses, including lupus, are possible. When present, the coexistence of these two etiologies can have a higher mortality than either disease alone. An underlying diagnosis of SLE should be considered in all patients presenting TTP and the study of this association may provide a better understanding of their immune-mediated pathophysiology.
We present the case of an 8-year-old girl with chronic idiopathic thrombocytopenic purpura (ITP) and a short history suggestive of raised intracranial pressure. Urgent computed tomography scan of the head showed a large bleed into a left cerebellar lesion. She underwent treatment with intravenous immunoglobulin (IVIg) and steroids to increase her platelet count, followed by excision of the lesion, which was found to be a benign pilocytic astrocytoma. The patient made a complete recovery and shortly afterwards underwent splenectomy, following which there was complete resolution of her thrombocytopenia.
A 15-year-old girl with a 9-year history of idiopathic thrombocytopenic purpura resistant to high-dose steroid therapy and to splenectomy was admitted to hospital at 35 weeks' gestation with a platelet count of 10 X 10(9)/L. The bleeding time was normal, and measures of platelet aggregation were nearly so. Treatment with high intravenous doses of polyvalent immune globulin led to a rise in the platelet count to more than 110 X 10(9)/L within 5 days. An elective cesarean section was performed through the lower uterine segment with good hemostasis. After delivery the platelet count fell to its former level, but no postpartum bleeding occurred. There was a brief episode of thrombocytopenia in the infant, with some petechiae but no other hemorrhagic manifestations. No untoward effects of the immune globulin infusion were observed in either mother or daughter.
Eltrombopag is one of a number of novel agents recently developed for use in the treatment of patients with immune thrombocytopenia (ITP). Rather than preventing destruction of platelets, these agents increase the production of platelets, presumably overwhelming the immune system resulting in normal platelet counts in individuals refractory to or dependent on other therapies. These treatments are well tolerated and in randomized controlled trials show an improvement in platelet counts and a reduction in bleeding in refractory patients. This article summarizes the development of this new class of drug and evaluates the safety and efficacy of eltrombopag in patients with ITP.
eltrombopag; immune thrombocytopenic purpura; thrombopoietin
Association of immune thrombocytopenic purpura and tuberculosis is a rare condition. In 5 patients presenting with this association, anti-tuberculous therapy was effective on both tuberculosis and thrombocytopenia suggesting a causal relationship between tuberculosis and immune thrombocytopenic purpura
immune thrombocytopenic purpura; immune; peripheral; thrombocytopenia
Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease.
We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease) and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital.
Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.
Macrolides have both immunomodulatory and antibacterial effects. We report 3 cases of primary immune thrombocytopenia (ITP) patients who were successfully treated with macrolides, irrespective of Helicobacter pylori (H. pylori) infection status. Case 1, an 88-year-old woman who was an H. pylori-positive ITP patient, was treated with clarithromycin (CAM). CAM was effective temporarily. As an alternative to CAM, she was successfully treated with erythromycin (EM) for more than 7 months. Case 2, a 61-year-old man who was an H. pylori-negative ITP patient, was unsuccessfully treated with CAM but successfully treated with EM. Case 3, a 75-year-old woman who was a H. pylori-negative ITP patient, was treated with CAM. CAM was effective temporarily. After approximately 6 months, she was treated with EM for a common cold, and her platelet count increased rapidly. Based on these findings, macrolide treatment was effective for ITP. The effectiveness of macrolides might suggest immunomodulatory effects as well as antibacterial effects for H. pylori.
Idiopathic thrombocytopenic purpura; Erythromycin; Macrolide
The first documented case of thrombotic thrombocytopenic purpura (TTP) associated with pneumococcal septicemia is reported. This association has been previously demonstrated with hemolytic uremic syndrome. The patient presented with recurrent seizures, oliguric renal failure, fever, thrombocytopenia and microangiopathic hemolytic anemia; coagulation studies were normal. Blood and sputum cultures were positive for Streptococcus pneumoniae. The patient responded to therapy with plasmapheresis and antiplatelet agents as well as antibiotics. Coincident infection should be searched for in all cases of TTP.
Plasmapheresis; Pneumococcal infections; Thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura (TTP) is a rare condition but associated with 90% mortality if left untreated. The diagnosis is usually made when there is thrombocytopenia and microangiopathic haemolytic anaemia, although the full pentad also includes fever, renal impairment, and neurological dysfunction. A variety of underlying causes have been implicated in acquired TTP including bacterial and viral infections, bone marrow and organ transplantation, pregnancy, immune disorders, and certain drugs. To date there is just one case report of TTP associated with statin treatment. The clinical course of a patient who presented with TTP after being started on simvastatin, a HMG-CoA inhibitor, is described.
There is emerging evidence that Hepatitis C virus (HCV) infection plays a role in the etiology of immune thrombocytopenia purpura (ITP) and autoimmune hemolytic anemia (AIHA) which both are severe autoimmune cytopenias.
In order to determine if HCV infection increases the risk for ITP and AIHA, we calculated the incidence rates of ITP and AIHA among 120,691 HCV-infected and 454,905 matched HCV-uninfected U.S. veterans diagnosed 1997–2004. After excluding individuals with a prior diagnosis of a lymphoproliferative disease, HIV, or cirrhosis, we fit Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) as measures of risks.
We found 296 ITP and 90 AIHA cases. Among HCV-infected versus HCV-uninfected persons, the overall incidence rates of ITP were 30.2 and 18.5 per 100,000 person-years, and for AIHA they were 11.4 and 5.0 per 100,000 person-years, respectively. HCV was associated with elevated risks for ITP (HR=1.8, 95% CI 1.4–2.3) and AIHA (HR=2.8, 95% CI 1.8–4.2). ITP incidence was increased among both untreated and treated HCV-infected persons (HR 1.7, 95% CI 1.3–2.2, and HR 2.4, 95% CI 1.5–3.7, respectively), whereas AIHA incidence was elevated only among treated HCV-infected persons (HR 11.6, 95% CI 7.0–19.3).
Individuals infected with HCV are at an increased risk for ITP, while the development of AIHA appears to be associated with HCV treatment. It may be beneficial to test individuals newly diagnosed with ITP for HCV infection.