scholarly journals Management of Vascular Thrombosis in Patients with Thrombocytopenia

2021 ◽  
Author(s):  
Minna Voigtlaender ◽  
Florian Langer

AbstractPlatelets play critical roles in hemostasis and thrombosis. While low platelet counts increase the risk of bleeding, antithrombotic drugs, including anticoagulants and antiplatelet agents, are used to treat thromboembolic events. Thus, the management of thrombosis in patients with low platelet counts is challenging with hardly any evidence available to guide treatment. Recognition of the underlying cause of thrombocytopenia is essential for assessing the bleeding risk and tailoring therapeutic options. A typical clinical scenario is the occurrence of venous thromboembolism (VTE) in cancer patients experiencing transient thrombocytopenia during myelosuppressive chemotherapy. In such patients, the severity of thrombocytopenia, thrombus burden, clinical symptoms, and the timing of VTE relative to thrombocytopenia must be considered. In clinical practice, distinct hematological disorders characterized by low platelet counts and a thrombogenic state require specific diagnostics and treatment. These include the antiphospholipid syndrome, heparin-induced thrombocytopenia (HIT) and (spontaneous) HIT syndromes, disseminated intravascular coagulation, and paroxysmal nocturnal hemoglobinuria.

Blood ◽  
2018 ◽  
Vol 131 (17) ◽  
pp. 1899-1902 ◽  
Author(s):  
Edward F. Plow ◽  
Yunmei Wang ◽  
Daniel I. Simon

Abstract Current antithrombotic drugs, including widely used antiplatelet agents and anticoagulants, are associated with significant bleeding risk. Emerging experimental evidence suggests that the molecular and cellular mechanisms of hemostasis and thrombosis can be separated, thereby increasing the possibility of new antithrombotic therapeutic targets with reduced bleeding risk. We review new coagulation and platelet targets and highlight the interaction between integrin αMβ2 (Mac-1, CD11b/CD18) on leukocytes and GPIbα on platelets that seems to distinguish thrombosis from hemostasis.


2010 ◽  
Vol 1 (3) ◽  
pp. 92-98
Author(s):  
Nadzeya Kuzniatsova ◽  
Gregory YH Lip

Antithrombotic drugs are prescribed more and more often in medical practice. With a progressively aging population, the proportion of patients having prothrombotic medical conditions such as coronary artery disease, atrial fibrillation, venous thrombosis and many others increases dramatically. Anticoagulants or antiplatelet agents save thousands of lives annually but also introduce concerns of increased risk of bleeding, especially in the settings of elective surgery or invasive procedures.


Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 357
Author(s):  
Gabriele Savioli ◽  
Iride Francesca Ceresa ◽  
Sabino Luzzi ◽  
Alice Giotta Lucifero ◽  
Maria Serena Pioli Di Marco ◽  
...  

Background and objectives: In patients who receive antiplatelet therapy (APT), the bleeding risk profile after mild head trauma (MHT) still needs clarification. Some studies have demonstrated an association with bleeding risk, whereas others have not. We studied the population of our level II emergency department (ED) trauma center to determine the risk of bleeding in patients receiving APT and whether bleeding results not from antiplatelet agents but rather from age. We assessed the bleeding risk, the incidence of intracranial hemorrhage (ICH) that necessitated hospitalization for observation, the need for cranial neurosurgery, the severity of the patient’s condition at discharge, and the frequency of ED revisits for head trauma in patients receiving APT. Materials and Methods: This retrospective single-center study included 483 patients receiving APT who were in the ED for MHT in 2019. The control group consisted of 1443 patients in the ED with MHT over the same period who were not receiving APT or anticoagulant therapy. Our ED diagnostic therapeutic protocol mandates both triage and the medical examination to identify patients with MHT who are taking any anticoagulant or APT. Results: APT was not significantly associated with bleeding risk (p > 0.05); as a risk factor, age was significantly associated with the risk of bleeding, even after adjustment for therapy. Patients receiving APT had a greater need of surgery (1.2% vs. 0.4%; p < 0.0001) and a higher rate of hospitalization (52.9% vs. 37.4%; p < 0.0001), and their clinical condition was more severe (evaluated according to the exit code value on a one-dimensional quantitative five-point numerical scale) at the time of discharge (p = 0.013). The frequency of ED revisits due to head trauma did not differ between the two groups. Conclusions: The risk of bleeding in patients receiving APT who had MHT was no higher than that in the control group. However, the clinical condition of patients receiving APT, including hospital admission for ICH monitoring and cranial neurosurgical interventions, was more severe.


2009 ◽  
Vol 29 (03) ◽  
pp. 274-278 ◽  
Author(s):  
U. Steigerwald ◽  
U. Walter ◽  
J. Kössler

SummaryInhibition of platelet function plays an important role in the treatment and secondary prevention of cardiovascular or cerebrovascular ischemic diseases. Established antiplatelet agents use different pharmacological targets for this role. Acetylic salicylic acid achieves a reduction of thromboxane A2 formation by inhibition of COX-1. Ticlopidin or clopidogrel are ADP-P2Y12 receptor antagonists. Tirofiban, abciximab or eptifibatid are used for the inhibition of the glycoprotein IIb/IIIa receptor which is activated at the surface of platelets preceding the final step of their aggregation. The mechanism of dipyridamole is based on the inhibition of adenosine uptake and of phosphodiesterase-5.Efforts are made to improve antiplatetelet therapy with the aim to find agents with favorable clinical outcome and lower bleeding risk. Current clinical studies focus on a new generation of ADP receptor antagonists (prasugrel, cangrelor and ticagrelor) as successors of ticlopidin and clopidogrel after coronary arterial interventions. Developments using platelet targets different from established drugs are thrombin receptor antagonists (like SCH530348) or thromboxane receptor antagonists (like S18886/terutroban) in patients with cerebrovascular events. Results from recent experimental studies could lead to new strategies for antiplatetelet therapy (like inhibition of GP Ib receptor, GP VI receptor, platelet-leukocyte interaction, factor XII and others) in the future.


1996 ◽  
Vol 76 (05) ◽  
pp. 682-688 ◽  
Author(s):  
Jos P J Wester ◽  
Harold W de Valk ◽  
Karel H Nieuwenhuis ◽  
Catherine B Brouwer ◽  
Yolanda van der Graaf ◽  
...  

Summary Objective: Identification of risk factors for bleeding and prospective evaluation of two bleeding risk scores in the treatment of acute venous thromboembolism. Design: Secondary analysis of a prospective, randomized, assessor-blind, multicenter clinical trial. Setting: One university and 2 regional teaching hospitals. Patients: 188 patients treated with heparin or danaparoid for acute venous thromboembolism. Measurements: The presenting clinical features, the doses of the drugs, and the anticoagulant responses were analyzed using univariate and multivariate logistic regression analysis in order to evaluate prognostic factors for bleeding. In addition, the recently developed Utrecht bleeding risk score and Landefeld bleeding risk index were evaluated prospectively. Results: Major bleeding occurred in 4 patients (2.1%) and minor bleeding in 101 patients (53.7%). For all (major and minor combined) bleeding, body surface area ≤2 m2 (odds ratio 2.3, 95% Cl 1.2-4.4; p = 0.01), and malignancy (odds ratio 2.4, 95% Cl 1.1-4.9; p = 0.02) were confirmed to be independent risk factors. An increased treatment-related risk of bleeding was observed in patients treated with high doses of heparin, independent of the concomitant activated partial thromboplastin time ratios. Both bleeding risk scores had low diagnostic value for bleeding in this sample of mainly minor bleeders. Conclusions: A small body surface area and malignancy were associated with a higher frequency of bleeding. The bleeding risk scores merely offer the clinician a general estimation of the risk of bleeding. In patients with a small body surface area or in patients with malignancy, it may be of interest to study whether limited dose reduction of the anticoagulant drug may cause less bleeding without affecting efficacy.


1999 ◽  
Vol 19 (04) ◽  
pp. 168-175 ◽  
Author(s):  
M. Weippert-Kretschmer ◽  
V. Kretschmer

SummaryPerioperative bleeding complications due to disorders of primary haemostasis are often underestimated. Routine determination of primary haemostasis is still problematic. The in vivo bleeding time (BT) shows low sensitivity and high variability. In this contribution the results and experiences with the IVBT having been obtained in various studies and during 10 years of routine use are reported. Patients and Methods: Blood donors before and after ASA ingestion, patients with thrombocytopenia as well as congenital and acquired platelet function disorders. Monitoring of desmopressin efficacy. IVBT with Thrombostat 4000 (tests with CaCl2 = TST-CaCl2 and ADP = TST-ADP) and PFA-100 (test cartridges with epinephrine = PFA-EPI and ADP = PFA-ADP). Results and Conclusions: IVBT becomes abnormal with platelet counts <100,000/μl. With platelet counts <50,000/μl the results are mostly outside the methodical range. IVBT proved clearly superior to BT in von Willebrand syndrome (vWS). All 16 patients with vWS were detected by PFA-EPI, whereas with BT 7 of 10 patients with moderate and 1 of 6 patients with mild forms of vWS were spotted. The majority of acquired and congenital platelet function disorders with relevant bleeding tendency were detectable by IVBT. Sometimes diagnostic problems arose in case of storage pool defect. Four to 12 h after ingestion of a single dose of 100 mg ASA the TST-CaCl2 became abnormal in all cases, the PFA-EPI only in 80%. However, the ASA sensitivity of TST-CaCl2 proved even too high when looking for perioperative bleeding complications in an urological study. Therefore, the lower ASS sensitivity of the PFA-100 seems to be rather advantageous for the estimation of a real bleeding risk. The good efficacy of desmopressin in the majority of cases with mild thrombocytopenia, congenital and acquired platelet function disorders and even ASS-induced platelet dysfunction could be proven by means of the IVBT. Thus IVBT may help to increase the reliability of the therapy. However, the IVBT with the PFA-100 is not yet fully developed. Nevertheless, routine use can be recommended when special methodical guidelines are followed.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Tseng ◽  
S Bhatt ◽  
M Girardo ◽  
D Liedl ◽  
P Wennberg ◽  
...  

Abstract Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None


Blood ◽  
2012 ◽  
Vol 120 (4) ◽  
pp. 748-760 ◽  
Author(s):  
Cassandra D. Josephson ◽  
Suzanne Granger ◽  
Susan F. Assmann ◽  
Marta-Inés Castillejo ◽  
Ronald G. Strauss ◽  
...  

Age-group analyses were conducted of patients in the prophylactic platelet dose trial (PLADO), which evaluated the relation between platelet dose per transfusion and bleeding. Hospitalized patients with treatment-induced hypoproliferative thrombocytopenia were randomly assigned to 1 of 3 platelet doses: 1.1 × 1011, 2.2 × 1011, or 4.4 × 1011 platelets/m2 per transfusion, given for morning counts of ≤ 10 000 platelets/μL. Daily hemostatic assessments were performed. The primary end point (percentage of patients who developed grade 2 or higher World Health Organization bleeding) was evaluated in 198 children (0-18 years) and 1044 adults. Although platelet dose did not predict bleeding for any age group, children overall had a significantly higher risk of grade 2 or higher bleeding than adults (86%, 88%, 77% vs 67% of patients aged 0-5 years, 6-12 years, 13-18 years, vs adults, respectively) and more days with grade 2 or higher bleeding (median, 3 days in each pediatric group vs 1 day in adults; P < .001). The effect of age on bleeding differed by disease treatment category and was most pronounced among autologous transplant recipients. Pediatric subjects were at higher risk of bleeding over a wide range of platelet counts, indicating that their excess bleeding risk may be because of factors other than platelet counts. This trial was registered at www.clinicaltrials.gov as #NCT00128713.


2021 ◽  
Vol 27 ◽  
pp. 107602962199647
Author(s):  
Kaitlyn C. Dykes ◽  
Cassandra A. Johnson ◽  
Jerald Z. Gong ◽  
Steven E. McKenzie ◽  
Holleh D. Husseinzadeh

Empiric management in suspected heparin-induced thrombocytopenia (HIT) is challenging due to imperfect prediction models, latency while awaiting test results and risks of empiric therapies. When there is high clinical suspicion for HIT, cessation of heparin and empiric non-heparin anticoagulation with FDA-approved argatroban is recommended. Alternatively off-label fondaparinux or watchful waiting have been utilized in clinical practice. Outcomes of patients empirically managed for HIT have not been compared directly in clinical trials and patients that ultimately do not have HIT are often overlooked. Clinicians need studies investigating empiric management to guide decision making in suspected HIT. In this study, adverse events (AE) were categorized and compared in patients being evaluated for HIT while undergoing empiric management by non-heparin anticoagulation with argatroban or fondaparinux, both at therapeutic or reduced doses, or watchful waiting with or without heparin. AE were defined as new thrombosis confirmed on imaging or new bleeding event after HIT was first suspected. A retrospective chart review of 312 patients tested for HIT at an academic hospital was conducted. 170 patients met inclusion criteria. Patients were excluded if the 4Ts score was < 4. The 4Ts score is a pretest probability for HIT based on thrombocytopenia degree, timing, alternative causes and presence of thrombosis. Included patients were divided according to management groups and compared with logistic regression analysis. Bleeding risk significantly differed between management groups (p = 0.002). Despite adjustment for bleeding risk, fondaparinux was associated with increased AE, (p = 0.03, OR = 5.81), while argatroban was not. There was no difference in AE based on time to initiation of empiric treatment and no advantage to reduced dosing with either anticoagulant. These findings challenge assumptions surrounding empiric HIT management.


2018 ◽  
Vol 22 (4) ◽  
Author(s):  
Anna Dusza ◽  
Michał Matysiak

In this article we present current investigation on primary immune thrombocytopenia in children. There are described pathomorphology, clinical symptoms, diagnosis and treatment. We also present current data from literature about genetic tests and latest data on treating options in children. Primary immune thrombocytopenia (ITP) is one of the most frequent hematological disorders in pediatric population. Although the majority of children have a self-limited and short duration of the disease. However, approximately 20-30% of those patients can develop chronic ITP, which can cause significant complications and higher mortality and reduced quality of life. Especially regarding to long-term immunosupression or surgical interventions, such like splenectomy and restrictions on daily activities to avoid trauma. Over the past decades a lot of informations has been reported about pathogenic features of ITP. Nowdays, we know that it is not only caused by increased platet destruction and decreased platet production, but also complex, multifactorial immune dysregulation, like loss of immune tolerance and generation of platelet autoantibodies. In this article we present current investigation on ITP including clinical symptoms, diagnosis, pathomorphology and latests options on treatment in children. We also present current data about genetic biomarker, such as Vanin-1 (VNN-1) which has been suggested as one of predictors of chronic disease and potentially can offer early prognosis estimation.


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