scholarly journals Thrombosis in Patients with Immune Thrombocytopenia ,Review of Literature

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-10
Author(s):  
Maimoonah Rasheed ◽  
Ashraf Tawfiq Soliman ◽  
Mohamed A Yassin

Introduction ITP is characterized by low platelet count due to immune mediated destruction and bleeding tendency. However, during last few decades thromboembolic events have been reported in patients with ITP. This review is done to study the reported cases of thromboembolic phenomenon in patient with ITP in an attempt to assess the patient characteristics and to understand the underlying mechanism. Methods We searched google Scholar, PubMed about cases with ITP and thrombosis the summary is presented in the following table (Table 1). Results Around 30 reported cases of ITP with thrombotic events were identified and a total of 36 events were recognized in last 10 years. The ages ranged from 3 years to 81 years with a mean of 51 years. Most of the patients were young and middle aged (18-65 years of age), meanwhile around 9 patients were elderly (age > 65 years). Only 3 cases were observed in pediatric age. Almost equal incidence in both genders was recognized. Half of the patient had chronic ITP while in the rest it was diagnosed less than a year. 20 out of 36 (55.6%) events happened at platelet count less than 100*10^9. While 16 events were reported with platelet count higher than this or unknown. Majority of the patients (around 64%) developed arterial events while fewer developed venous thrombosis. For treatment, most of the patients (44%) were not receiving any particular treatment for ITP at the time of thrombotic event. While 6 events (17%) happened while being treated with IVIG and 10 events (28%') happened while on TPO-RA. Only 3 patients were treated with corticosteroids prior to the event. In patients treated with TPO-RAs arterial and venous events were almost similar (57% vs 43% respectively) while majority of the events happened at lower than normal platelet count (7/10 events). Almost half of the patients had one or more underlying risk factor predisposing to atherosclerosis and thrombosis. Most of the patients were treated appropriately for the events with either antiplatelet agents or anticoagulation while simultaneously treatment for ITP was given. Corticosteroids were most frequently used for ITP during the episode followed by IVIG (52% and 28% of total treated patients respectively). Only 1 patient was treated with TPO-RA after the event for low platelet counts while others received other treatments (Rituximab, Danazol and splenectomy). Discussion Thrombosis is a complex process involving arteries and veins. Accelerated atherosclerosis and plaque rupture is the underlying event for arterial thrombosis. While in venous thrombosis immobility and procoagulant states are the main factors. Immune thrombocytopenia is characterized by immune mediated destruction and impaired production of platelets predisposing to bleeding mostly. However, it is a unique pathological process that is linked to both bleeding and thrombosis. Multiple factors predispose patients to thrombosis in ITP. The patients with chronic and active disease are particularly at risk of paradoxical thrombosis due to accelerated atherosclerosis as in other autoimmune conditions, predisposing to arterial thrombotic events. Active disease is also characterized by increased turnover of platelets in bone marrow and higher levels of circulating platelets microparticles (PMPs) which promote thrombin formation and promote venous thrombosis. The patients treated with IVIG and TPO-RA are at higher risk as compared to other forms of treatment. IVIG is used in acute states as it prevents the destruction of platelets but simultaneously promotes thrombosis by increasing blood viscosity and thrombin production. TPO-RAs are agents which mimic the action of thrombopoietin on megakaryocytes promoting their growth and differentiation and increasing platelet production. Increasing platelet count above the normal target might contribute to thrombosis however megakaryocyte activation itself leads to increased risk of thrombosis, despite low platelet count. In patients with ITP and thrombotic events, judicious use of antiplatelet therapy and anticoagulation is indicated along with simultaneous therapy directed at improving platelet count. Conclusion Patient with active ITP are predisposed to thrombosis in addition to bleeding. A treating physician needs to be vigilant to diagnose early the events and then to institute proper use of antiplatelets and anticoagulation along with therapy directed at ITP. Figure Disclosures No relevant conflicts of interest to declare.

Author(s):  
Tanwi Singh ◽  
Anshuman Sinha

The major risk associated with low platelet count in pregnancy is the increased risk of bleeding during the childbirth or post that. There is an increased blood supply to the uterus during pregnancy and the surgical procedure requires cutting of major blood vessels. Women with thrombocytopenia are at increased risk of losing excessive blood. The risk is more in case of caesarean delivery as compared to vaginal delivery. Hence based on above findings the present study was planned for Assessment of the Platelet Count in the Pregnant Women in IGIMS, Patna, Bihar. The present study was planned in Department of Pathology, Indira Gandhi Institute of Medical Science, Patna, Bihar, India. The present study was planned from duration of January 2019 to June 2019. In the present study 200 pregnant females samples received for the platelet estimation were enrolled in the present study. Clinically platelet indices can be a useful screening test for early identification of preeclampsia and eclampsia. Also platelet indices can assess the prognosis of this disease in pregnant women and can be used as an effective prognostic marker because it correlates with severity of the disease. Platelet count is a simple, low cost, and rapid routine screening test. Hence the data generated from the present study concludes that platelet count can be used as a simple and cost effective tool to monitor the progression of preeclampsia, thereby preventing complications to develop during the gestational period. Keywords: Platelet Count, Pregnant Women, IGIMS, Patna, Bihar, etc.


2021 ◽  
Vol 104 (4) ◽  
pp. 672-675

The present case series described six chronic immune thrombocytopenia patients (cITP), with a median age of 7.7 (7.0 to 13.0) years and low platelet count at 15,500 (7,000 to 20,000)/uL. They were suffering from bleeding symptoms and side effects of treatment. After enrollment, they were treated with thrombopoietin receptor agonist (eltrombopag). Five patients responded positively, showing a median platelet count of 115,000 (39,000 to 433,000)/uL. The median dose of eltrombopag used was 1.3 (0.8 to 2.2) mg/kg/day. The quality of life (QoL) improved for all patients, with their median overall score using a Pediatric QoL questionnaire showing 25.0% improvement. Median scores also showed improvements in each sphere of life functioning as physical (30.8%), emotional (26.4%), social (16.4%), and school (21.4%). The present report demonstrated that a select group of cITP patients, with low platelet count and bleeding symptoms, benefitted from treatment with eltrombopag, as shown by increased platelet counts and improved QoL. Keywords: Chronic ITP, Thrombopoietin receptor agonist, Children


Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas L. Ortel

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.


2019 ◽  
Vol 7 ◽  
pp. 2050313X1984052
Author(s):  
Dawid Ilnicki ◽  
Rafał Wyderka ◽  
Przemysław Nowicki ◽  
Alicja Sołtowska ◽  
Jakub Adamowicz ◽  
...  

The objective of this case report is to present how the chronic condition significantly complicates life-saving procedures and influences further treatment decisions. A 64-year-old man suffering from arterial hypertension and immune thrombocytopenic purpura presented to the Emergency Department with anterior ST-elevation myocardial infarction. An immediate coronary angiography was performed where critical stenosis of the proximal left anterior descending was found. It was followed by primary percutaneous intervention with bare metal stent. In first laboratory results, extremely low platelet count was found (13 × 109/L). Consulting haematologist advised the use of single antiplatelet therapy and from the second day of hospitalisation only clopidogrel was prescribed. On the sixth day of hospital stay, patient presented acute chest pain with ST elevation in anterior leads. Emergency coronary angiography confirmed acute stent thrombosis and aspiration thrombectomy was performed. It was therefore agreed to continue dual antiplatelet therapy for 4 weeks. As there are no clinical trials where patients with low platelet count are included, all therapeutic decisions must be made based on clinician’s experience and experts’ consensus. Both the risk of haemorrhagic complications and increased risk of thrombosis must be taken into consideration when deciding on patient’s treatment.


1981 ◽  
Author(s):  
F Frassoni ◽  
F Piovella ◽  
C Castagnola ◽  
P Almasio ◽  
M M Ricetti ◽  
...  

Results of an investigation concerning a familial thrombocytopenia with morphological abnormalities of bone marrow megakaryocytes and moderate bleeding tendency are presented. The laboratory and clinical data of a young woman and her mother are described. Both patients presented orolonged bleeding time which correlated with a low platelet count and which was not asso ciated with morphological or functional platelet impairment or plasmatic factors defects. Examination of bone marrow aspirates of both proposita revealed the presence of unusual features.Smears revealed a great increase of megakaryo cyte count and most of them had the appearance of micromegakaryocytes. The nature of these celi was confirmed by immunofluorescence for factor VIII-related antigen and fibronectin. Electron microscopy performed on megakaryocytes showed the presence of a wide peripheral area of amornhous substance, while platelet ultrastructure did not show any abnormality.


Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1504-1508 ◽  
Author(s):  
FR Rosendaal ◽  
T Koster ◽  
JP Vandenbroucke ◽  
PH Reitsma

Resistance to activated protein C (APC) is a common inherited risk factor for venous thrombosis, which is associated with a mutation in coagulation factor V (factor V Leiden). We investigated the risk of venous thrombosis in individuals homozygous for this abnormality. We determined the factor V Leiden genotype in 471 consecutive patients aged less than 70 years with a first objectively confirmed deep-vein thrombosis and in 474 healthy controls. We found 85 heterozygous and seven homozygous individuals among the cases with thrombosis and 14 heterozygous individuals among the control subjects. The expected number of homozygous individuals among the controls was calculated from Hardy-Weinberg equilibrium and estimated at 0.107 (allele frequency, 1.5%). Whereas the relative risk was increased sevenfold for heterozygous individuals, it was increased 80-fold for homozygous individuals. These patients experienced their thrombosis at a much younger age (31 v 44 years). The homozygous individuals were predominantly women, most likely due to the effect of oral contraceptives. Because of the increased risk of thrombosis with age, the absolute risk becomes most pronounced in older patients, both for heterozygous and homozygous individuals. For the homozygous individuals, the absolute risk may become several percentage points per year. This implies that most individuals homozygous for factor V Leiden will experience at least one thrombotic event in their lifetime.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2194-2194
Author(s):  
Takayuki Saitoh ◽  
Chiaki Ushie ◽  
Atsushi Iwasaki ◽  
Norihiko Moriyama ◽  
Tomonori Takani ◽  
...  

Abstract Abstract 2194 Introduction: The severity of immune thrombocytopenia (ITP) depends on the degree of the thrombocytopenia and the extent of bleeding. Some investigators have reported the association between the thrombocytopenia and cytokine dysregulation in ITP. We investigated the association between the severity of thrombocytopenia at diagnosis in ITP patients and several cytokine polymorphisms, including IL-10-1082A/G, -819T/C, -592A/C, IL-17F-7488T/C and IL-18-607A/C, −137G/C. Patients and methods: We examined 102 patients (male/female, 24/78; median age, 42) diagnosed with chronic ITP. The definition, response criteria, including complete response (CR)and response (R), loss of CR,and “corticosteroid-dependence” were assessed according to the criteria of the ITP International Working Group. ITP with severe thrombocytopenia (ST group)was defined as thrombocytopenia (platelet count < 10×109/L) at the initial diagnosis of ITP. Genotyping of IL-10 (rs1800870 − 1082 A/G, rs1800871 − 819 T/C, and rs1800872 − 592 A/C) and IL-17F (rs763780, 7488 T/C) polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the genotyping of the IL-18 polymorphism (rs187238 −137G/C and rs1946518−607 A/C) was determined by the allelic specific polymerase chain reaction technique. To confirm the accuracy of the assay, amplification products of several individuals were sequenced using an ABI Prism Genetic Analyzer. Genotype and allele frequencies were compared between the study groups using χ2-test. The characteristics and laboratory features of ITP patients with each polymorphisms were compared using χ2-tests and student t-tests. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated for each study. All patients were provided written information about the study. This study was approved by the Institutional Research Board of Gunma University Hospital. Results: Clinical features of chronic ITP: The platelet count ranged from 1×109/L to 98×109/L with a mean of platelet count of 32×109/L at the initial diagnosis. Fifty seven patients (49%) had bleeding tendency. Steroid treatment was given to 68 patients (66.7%) and eradication of Helicobacter pylori (H. pylori) was performed in 32 patients (31.4%), while splenectomy was performed in only 11 patients (10.8%). Clinical features of ST group vs. non-ST group in chronic ITP: Of these 102 patients, 17 (16.7%) had severe thrombocytopenia (platelet count < 10×109/L) (ST group). ST group were significantly older (ST group: median 59 years vs. non-ST group: 41 years, p<0.01) and had more severe bleeding tendency (ST group: 100% vs. non-ST group: 54%, p<0.0001). Steroid treatment was frequently given to ST group than to non-ST group (ST group: 100% vs. non-ST group: 59.5%, p<0.001). Though the response to corticosteroids treatment was not significantly different between ST group and non-ST group (CR rate, ST group: 50% vs. non-ST group: 51.0%, p=0.94), corticosteroid-dependent patients in ST group was significantly higher than in non-ST group (76.9% vs. 25.3%, p<0.005). Polymorphism study of ST group vs. non-ST group in chronic ITP: The frequencies of genotypes of cytokines in patients with chronic ITP according to the definition of criteria of ST were as follows: AA (93.3% vs. 97.1%) and AG (6.7% vs. 2.9%, p=0.48) for IL-10–1082; TT (46.7% vs. 33.3%), TC (33.3% vs.55 %) and CC (20% vs. 11.7%) for IL-10–819; AA (46.7% vs. 33.3%), AC (33.3% vs.55 %) and CC (12.2% vs. 11.5%) for IL-10–592; TT (100% vs. 81%) and TC (0% vs. 19%) for IL-17F; GG (82.4% vs. 74.4%), GC (17.6% vs. 23.2%) and CC (0% vs. 2.4%) for IL-18–137; AA (35.3% vs. 34.1%), AC (58.8% vs. 53.7%) and CC (5.9% vs 12.2%) for IL-18–607 loci (ST group vs. non-ST group, respectively). No significant difference was observed between ST group and non-ST group according to IL-10–1082A/G, −819T/C, −592A/C, and IL-18–607A/C, −137G/C polymorphism. However, the numbers of IL-17F 7488TT genotype (higher function type) in ST group were significantly higher than in non-ST group (ST group: 100% vs. non-ST group: 81% p<0.05). Conclusion: These findings suggest that severe thrombocytopenia at diagnosis have an impact of bleeding tendency and corticosteroid-dependency of chronic ITP. Furthermore, IL-17F polymorphism may affect the severity of thrombocytopenia of chronic ITP. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2783-2783
Author(s):  
Eva Zetterberg ◽  
Margareta S Carlsson Alle ◽  
Juliane Najm ◽  
Andreas Greinacher

Abstract MYH-9 related platelet disorders are inherited macrothrombocytopenias. Before the genetic cause was identified, four overlapping syndromes (May-Hegglin, Epstein, Fechtnerand Sebastian syndrome) described the additional clinical manifestations in MYH-9 disorders including renal failure, hearing loss, pre senile cataract and inclusion bodies in leucocytes that are present in different combinations. The MYH-9-gene codes for the cytoplasmic contractile protein non muscular myosin heavy chain IIA, present in several tissues, which explains the additional symptoms. The bleeding tendency is usually mild to moderate but rarely, thrombotic complications are also seen (1). We report on the thrombin generation potential (ETP) in MYH9 patients with and without arterial thrombosis. In the first family (family A) 4 members were evaluated: a 51 year old woman (platelet count 36), her 24 year old daughter (platelet count 46), and the brother of the woman (57 years; platelet count 39) and his 30 year old son (platelet count 44). All four were affected by MYH-9 disorder with macrothrombocytopenia and inclusion bodies in the leucocytes and a 5521G>A mutation, causing Glu1841Lys. 3 of them had a moderate bleeding tendency [ISTH /SSC bleeding scores 9, 13, 4 where <4 is normal) (3)] and in the 51 year old women and her brother, renal insufficiency and hearing loss were already present. Both patients had an arterial thrombosis (myocardial infarction and pons infarction respectively) before 50 year of age. Both showed hyperlipidemia and hyperhomocysteinemia. In the second family (Family B) macrothrombocytopenia and small to medium size inclusion bodies in the leucocytes were found in the mother (38 years; platelet count 36) and the daughter (age15 years, platelet count 46) caused by a c. 4679 T>G mutation resulting in p.Val1560Gly. Their bleeding tendency was mild (bleeding scores 4 and 3 respectively). Thrombelastography (ROTEM) was normal in all five individuals. ETP was seen to be below the normal range in family B. However, in family A, the two members affected by thrombosis had a normal ETP (Fig 1), indicating that other factors compensated for the low platelet count and clinically even led to a breakthrough of arterial thrombosis despite the low platelet count. We suggest that other centers also assess the ETP in their MYH-9 patients according tour protocol to gather data on the potential association of the ETP with the phenotype. References Althaus K, Greinacher A: MYH-9 Related Platelet Disorders: Strategies for Management and Diagnosis. Transfus Med Hemother. 2010 October; 37(5): 260–267. Girolami A , Vettore S, Bonamigo E, Fabris F: Thrombotic events in MYH9 gene-related autosomal macrothrombocytopenias (old May–Hegglin, Sebastian, Fechtner and Epstein syndromes) J Thromb Thrombolysis. 2011 Nov;32(4):474-73. Rodeghiero F, Tosetto A, Abshire T et al.; ISTH/SSC Joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessmenttool: a standardizedquestionnaire and a proposal for a newbleedingscore for inherited bleeding disorders. J Thromb Haemost 2010; 8: 2063–5. Figure 1. Endogenous thrombin potential in two families with MYH-9 related disease Figure 1. Endogenous thrombin potential in two families with MYH-9 related disease Thrombin generation was performed on frozen platelet rich plasma on 5 members from two different families (family A and B) with MYH-9 related disease. Two members in the first family (A:1 and A:2) had a previous arterial thrombosis (pons infarction and myocardial infarction, respectively, marked with a star). Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Judy Ibrahim ◽  
Mohammad Alashqar ◽  
Shamma Al Zaabi ◽  
Omar Trad ◽  
Amar Al Shibli

Immune thrombocytopenia (ITP) is a disorder characterized by immune-mediated destruction of thrombocytes leading to peripheral blood platelet count of <100 × 10^9/L. Primary ITP is a terminology used in the absence of other causes or disorders that may be associated with thrombocytopenia, i.e., isolated thrombocytopenia. The term secondary ITP is used if such diseases coexist. We present here a case of a 14-year-old female diagnosed with immune thrombocytopenia. When her evaluation was not strongly supportive of primary ITP, she was screened and proved to have a concomitant Hashimoto thyroiditis. Contrary to the popular belief about secondary ITP in adult population, treatment of our patient’s hypothyroidism did not improve her platelet’s count, and the patient needed multiple immunosuppressive medications to improve her condition.


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