Individualized Bleeding Risk Assessment through Thromboelastography: A Case Report of May–Hegglin Anomaly in Preterm Twin Neonates

May–Hegglin anomaly (MHA) is a rare autosomal dominant disorder in the spectrum of myosin heavy chain-related disorders (MYH9-RD), characterized by congenital macrothrombocytopenia and white blood cell inclusions. MHA carries a potential risk of hemorrhagic complications. Bleeding diathesis is usually mild, but sporadic, life-threatening events have been reported. Data regarding the clinical course and outcomes of neonatal MYH9-RD are limited, and specific guidelines on platelet transfusion in asymptomatic patients are lacking. We present monochorionic twins born preterm at 32 weeks of gestation to an MHA mother; both presented with severe thrombocytopenia at birth. Peripheral blood smear demonstrated the presence of macrothrombocytes, and immunofluorescence confirmed the diagnosis of MHA. Close clinical monitoring excluded bleeding complications, and serial hemostatic assessments through a viscoelastic system demonstrated functionally normal primary hemostasis in both patients. Therefore, prophylactic platelet transfusions were avoided. Whole DNA sequencing confirmed the pathogenetic variant of MHA of maternal origin in both twins. Thromboelastography allowed real-time bedside bleeding risk assessment and supported individualized transfusion management in preterm newborns at risk of hemostatic impairment. This report suggests that dynamic and appropriate clotting monitoring may contribute to the more rational use of platelets’ transfusions while preserving patients with hemorrhagic complications and potential transfusion-related side effects.

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Can Immature Platelet Fraction (IPF) be Used to Assess Bleeding Risk in Pediatric Immune Thrombocytopenia (ITP) and to Differentiate ITP from Bone Marrow Failure/Aplastic Anemia? A Retrospective Analysis

Blood ◽

10.1182/blood.v126.23.3474.3474 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3474-3474 ◽

Cited By ~ 1

Author(s):

Karen Lee Bride ◽

Derick Lim ◽

Michele Paessler ◽

Michele P Lambert

Keyword(s):

Bone Marrow ◽

Platelet Count ◽

Immune Thrombocytopenia ◽

Bone Marrow Failure ◽

Bleeding Risk ◽

Medical Laboratory ◽

Bleeding Complications ◽

Severe Thrombocytopenia ◽

Immature Platelet Fraction ◽

Time Of Presentation

Abstract Immune Thrombocytopenia (ITP) usually presents with isolated, severe thrombocytopenia with very low platelet count (generally less than <30 x 109/L) in the absence of other hematologic abnormalities. However, ITP is a diagnosis of exclusion without any definite diagnostic test that can confirm the diagnosis at the time of presentation and clinicians occasionally worry at the time of presentation about other bone marrow processes that may present with thrombocytopenia, which would require considerably different therapy. In light of current guidelines suggesting that observation is likely to be safe in pediatric patients with low platelet counts without significant bleeding, identifying patients at risk for severe hemorrhage is even more important to help guide therapy. In addition, appropriately differentiating ITP from other diagnoses may also prevent inappropriate administration of ineffective therapies. The immature platelet fraction (IPF) is a measure of platelet turnover measuring RNA containing, large platelets by fluorescently labeling the platelets and utilizing flow cytometric gates programmed into the Sysmex XN-3000 hematology analyzer. We examined the medical laboratory records of 134 patients who had an IPF performed over the past 4 months for correlation between IPF and bleeding manifestations. In ITP patients who presented with significant bleeding symptoms (defined as epistaxis which was more than brief, oral bleeding more than palatal petechiae or GI or intracranial hemorrhage), the IPF was significantly lower than in those who presented with no bleeding or cutaneous bleeding only (bruising and petechiae): IPF=4.3%±1.6 SEM in bleeding patients versus 21.8%±1.8 SEM in not bleeding patients; p<0.0001. In two patients with life threatening hemorrhage and ITP (GI bleeding with drop in hemoglobin requiring both PRBC transfusion and treatment to raise the platelet count; ICH resulting in mortality), the IPF was low at the time of initial hemorrhage, but increased after ITP therapy (GI Bleed: plt 1K, IPF 5.3% increased to 20.3% after IVIG; ICH plt 6K, IPF 1.8% increased to 12.8% after IVIG and prednisone). We also examined first platelet count and IPF in 127 patients with ITP and 21 patients with BMF/AA who presented to our institution since October 2013. In this cohort of patients, the IPF in patients with ITP was significantly higher than in the BMF/AA patients and an IPF of >5.3 was associated with a negative predictive value of 80% for BMF/AA (IPF 16.6%±1.2 SEM in ITP vs. 2.9%±1.4 SEM in BMF/AA). In summary, we demonstrate that the IPF is a useful and simple adjunct in diagnosis of ITP which can help differentiate the patients most likely to have ITP from those who may need further diagnostic evaluation and require treatment to prevent bleeding complications. Further studies will focus on the ability of the IPF to prospectively predict the bleeding risk of patients and categorize patients. Disclosures Lambert: GSK: Consultancy; NovoNordisk: Honoraria; Hardin Kundla McKeon & Poletto: Consultancy.

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Bleeding complications in immune thrombocytopenia

Hematology ◽

10.1182/asheducation-2015.1.237 ◽

2015 ◽

Vol 2015 (1) ◽

pp. 237-242 ◽

Cited By ~ 43

Author(s):

Donald M. Arnold

Keyword(s):

Platelet Count ◽

Clinical Studies ◽

Immune Thrombocytopenia ◽

Assessment Tool ◽

Bleeding Risk ◽

Administrative Databases ◽

Bleeding Complications ◽

Severe Bleeding ◽

Severe Thrombocytopenia ◽

Case Definitions

Abstract Bleeding manifestations in patients with immune thrombocytopenia (ITP) range from mild skin bruises to life-threatening intracranial hemorrhage (ICH). Severe bleeding is distinctly uncommon when the platelet count is >30 × 109/L and usually only occurs when the platelet count falls <10 × 109/L. Based on estimates from clinical studies, ITP registries and administrative databases, the frequency of ICH in patients with ITP is ∼0.5% in children and 1.5% in adults. Estimates of severe (non-ICH) bleeding are difficult to obtain because of the lack of standardized case definitions; the lack of a universally accepted, ITP-specific bleeding assessment tool; and the omission of reporting bleeding outcomes in many clinical studies. In practice, the presence of bleeding should dictate whether or not treatment is needed because many patients, especially children, can be safely managed with observation alone. Guiding principles for the management of ITP, based on the bleeding risk are: (1) Decide when treatment is needed and when it can safely be withheld; (2) for patients with chronic ITP, use the least toxic treatment at the lowest dose; (3) emergency treatment of severe thrombocytopenia-associated bleeding requires combination therapy; and (4) early aggressive therapy may result in durable platelet count responses.

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Prevalence, patterns, and factors associated with bleeding tendencies in dengue

The Journal of Infection in Developing Countries ◽

10.3855/jidc.5031 ◽

2015 ◽

Vol 9 (01) ◽

pp. 105-110 ◽

Cited By ~ 5

Author(s):

Emmanuel Bhaskar ◽

Gopalan Sowmya ◽

Swathy Moorthy ◽

Varun Sundar

Keyword(s):

Platelet Count ◽

Bleeding Risk ◽

International Normalized Ratio ◽

Drug Intake ◽

Bleeding Complications ◽

Study Cohort ◽

Severe Thrombocytopenia ◽

Factors Associated ◽

Platelet Counts ◽

Anti Platelet Drug

Introduction: The pattern of bleeding tendencies in dengue and its corellation with platelet count and other factors requires clarification. Methodology: A retrospective study on bleeding tendencies in adults with dengue and platelet counts of less than 100,000 per mm3 was conducted. Factors associated with bleeding were analyzed. The study cohort were grouped as dengue with severe thrombocytopenia when platelet count was < 50,000/mm3 and as dengue with moderate thrombocytopenia if platelet count was 50,000–100,000/mm3 Results: A total of 638 patients formed the study cohort. A 24.1% prevalence of bleeding tendencies was observed. Prior anti-platelet drug intake, platelet count of < 70,000/mm3, international normalized ratio > 2.0, and partial thromboplastin time > 60 seconds were associated with bleeding. Esophagogastroduodenoscopy was found to identify structural gastroduodenal lesions when dengue was complicated by hematemesis or melena. Conclusions: The results of this study suggest that bleeding complications in dengue can occur at platelet counts of up to 70,000/mm3, and that prior anti-platelet drug intake increases bleeding risk. Evaluation of hematemesis or melena in dengue with esophagogastroduodenoscopy is beneficial.

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Varicose vein surgery under anti-platelet therapy

Phlebologie ◽

10.1055/s-0037-1622242 ◽

2008 ◽

Vol 37 (06) ◽

pp. 287-297 ◽

Cited By ~ 1

Author(s):

P.-M. Baier ◽

Z. T. Miszczak

Keyword(s):

Varicose Vein ◽

Bleeding Time ◽

Varicose Veins ◽

Bleeding Risk ◽

Bleeding Complications ◽

Review Of The Literature ◽

Varicose Vein Surgery ◽

Anti Platelet Therapy ◽

Male Patients ◽

Acute Atherothrombosis

Summary Background: Platelet function inhibitors (PFI) are used for prophylaxis of atherothrombosis. These drugs cause a prolongation of the bleeding time and should eventually be stopped before an elective operation. However, there is a risk that a perioperative pause of PFI lead to acute atherothrombosis. Objective: Our aim was to study whether a discontinuation of PFI therapy is necessary to avoid bleeding complications in patients undergoing varicose vein surgery. Methods: Selective review of the literature and retrospective analysis of clinical data of our own patients. Results: In the years 2002 to 2007 a total of 10 827 patients have been operated on varicose veins, 673 (6.2%) of these aged 32–86 years (67 ± 7.9) receiving permanent PFI therapy: 256 male patients (38.0%) and 417 female (62.0%), 39.1% categorized as ASA III patients: male 11.6%, female 27.5%. 38 patients who continued PFI therapy did not demonstrate haemorrhagic complications and none of those pausing anti-platelet medication experienced thromboembolic complications. The literature survey confirmed our finding that it is not necessary to suspend PFI medication for varicose vein surgery as the bleeding risk can be controlled for by technical means. Conclusion: Discontinuation of PFI therapy prior to interventions on varicose veins does not seem to be necessary, further studies are essential though.

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Determination and Treatment of Disorders of Primary Haemostasis

Hämostaseologie ◽

10.1055/s-0038-1660415 ◽

1999 ◽

Vol 19 (04) ◽

pp. 168-175 ◽

Cited By ~ 6

Author(s):

M. Weippert-Kretschmer ◽

V. Kretschmer

Keyword(s):

Platelet Function ◽

Bleeding Risk ◽

Bleeding Complications ◽

Bleeding Tendency ◽

Platelet Counts ◽

Platelet Function Disorders ◽

Perioperative Bleeding ◽

Before And After ◽

Low Sensitivity

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.

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Immune Thrombocytopenia in an Adolescent with Hashimoto’s Thyroiditis – Case Report

Journal of Interdisciplinary Medicine ◽

10.2478/jim-2019-0018 ◽

2019 ◽

Vol 4 (3) ◽

pp. 145-149 ◽

Cited By ~ 1

Author(s):

Izabella Kelemen ◽

Zsuzsanna Erzsébet Papp ◽

Mária Adrienne Horváth

Keyword(s):

Platelet Count ◽

Autoimmune Diseases ◽

Hashimoto’S Thyroiditis ◽

Clinical Signs ◽

Immunoglobulin Therapy ◽

Peripheral Blood Smear ◽

Bleeding Complications ◽

Hashimoto's Thyroiditis ◽

Line Treatment ◽

First Line

Abstract Introduction: In childhood, thrombocytopenia caused by transient antibody-mediated thrombocyte destruction is most frequently diagnosed as immune thrombocytopenic purpura (ITP). We report the case of a girl with ITP associated with autoimmune thyroiditis. Case presentation: A 11-year-old female patient with Hashimoto’s thyroiditis presented with clinical signs of petechiae and ecchymoses on the extremities. Laboratory tests showed remarkable thrombocytopenia with a platelet count of 44,500/μL, hence she was referred to a hematologic consultation. The peripheral blood smear showed normal size platelets in very low range. The bone marrow examination exposed hyperplasia of the megakaryocyte series with outwardly morphologic abnormalities. The patient was diagnosed with ITP, and her first-line treatment was pulsed steroid and immunoglobulin therapy. The thrombocytopenia was refractory to these first-line medications. After 6 months of corticotherapy and a period of severe menorrhagia, azathioprine immunosupression was initiated as a second-line treatment. Her platelet count rapidly increased, and the evolution was good, without bleeding complications. Conclusion: In case of a medical history of autoimmune diseases and treatment-resistant ITP, attention must be focused on detecting coexisting autoimmune diseases and adjusting the treatment in accordance with the chronic evolution of the disease.

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Current management of cancer-associated venous thromboembolism in patients with thrombocytopenia: a retrospective cohort study

Internal and Emergency Medicine ◽

10.1007/s11739-021-02771-3 ◽

2021 ◽

Author(s):

Alessandro Squizzato ◽

Silvia Galliazzo ◽

Elena Rancan ◽

Marina Di Pilla ◽

Giorgia Micucci ◽

...

Keyword(s):

Platelet Count ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Cerebral Metastasis ◽

Bleeding Complications ◽

Severe Thrombocytopenia ◽

Regression Analyses ◽

Multivariate Logistic Regression ◽

Current Management

AbstractOptimal management of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is uncertain. We described current management and clinical outcomes of these patients. We retrospectively included a cohort of cancer patients with acute VTE and concomitant mild (platelet count 100,000–150,000/mm3), moderate (50,000–99,000/mm3), or severe thrombocytopenia (< 50,000/mm3). Univariate and multivariate logistic regression analyses explored the association between different therapeutic strategies and thrombocytopenia. The incidence of VTE and bleeding complications was collected at a 3-month follow-up. A total of 194 patients of whom 122 (62.89%) had mild, 51 (26.29%) moderate, and 22 (11.34%) severe thrombocytopenia were involved. At VTE diagnosis, a full therapeutic dose of LMWH was administered in 79.3, 62.8 and 4.6% of patients, respectively. Moderate (OR 0.30; 95% CI 0.12–0.75), severe thrombocytopenia (OR 0.01; 95% CI 0.00–0.08), and the presence of cerebral metastasis (OR 0.06; 95% CI 0.01–0.30) were independently associated with the prescription of subtherapeutic LMWH doses. Symptomatic VTE (OR 4.46; 95% CI 1.85–10.80) and pulmonary embolism (OR 2.76; 95% CI 1.09–6.94) were associated with the prescription of full therapeutic LMWH doses. Three-month incidence of VTE was 3.9% (95% CI 1.3–10.1), 8.5% (95% CI 2.8–21.3), 0% (95% CI 0.0–20.0) in patients with mild, moderate, and severe thrombocytopenia, respectively. The corresponding values for major bleeding and mortality were 1.9% (95% CI 0.3–7.4), 6.4% (95% CI 1.7–18.6), 0% (95% CI 0.0–20.0) and 9.6% (95% CI 5.0–17.4), 48.2% (95% CI 16.1–42.9), 20% (95% CI 6.6–44.3). In the absence of sound evidence, anticoagulation strategy of VTE in cancer patients with thrombocytopenia was tailored on an individual basis, taking into account not only the platelet count but also VTE presentation and the presence of cerebral metastasis.

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Higher anticoagulation targets and risk of thrombotic events in severe COVID-19 patients: bi-center cohort study

Annals of Intensive Care ◽

10.1186/s13613-021-00809-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Julie Helms ◽

◽

François Severac ◽

Hamid Merdji ◽

Maleka Schenck ◽

...

Keyword(s):

Cohort Study ◽

Mortality Rate ◽

Bleeding Risk ◽

Tertiary Hospital ◽

Biological Data ◽

Bleeding Complications ◽

Therapeutic Group ◽

Vein Thrombosis ◽

Icu Stay ◽

Thrombotic Complications

Abstract Background Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (ICUs) from two centers of a French tertiary hospital were included in our cohort study. Patients were compared according to their anticoagulant treatment to evaluate the risk/benefit of prophylactic anticoagulation versus therapeutic anticoagulation. Medical history, symptoms, biological data and imaging were prospectively collected. Results One hundred and seventy-nine patients (73% men) were analyzed: 108 in prophylactic group and 71 in therapeutic group. Median age and SAPS II were 62 [IQR 51; 70] years and 47 [IQR 37; 63] points. ICU mortality rate was 17.3%. Fifty-seven patients developed clinically relevant thrombotic complications during their ICU stay, less frequently in therapeutic group (adjusted OR 0.38 [0.14–0.94], p = 0.04). The occurrences of pulmonary embolism (PE), deep vein thrombosis (DVT) and ischemic stroke were significantly lower in the therapeutic group (respective adjusted OR for PE: 0.19 [0.03–0.81]; DVT: 0.13 [0.01–0.89], stroke: 0.06 [0–0.68], all p < 0.05). The occurrence of bleeding complications was not significantly different between groups, neither were ICU length of stay or mortality rate. D-dimer levels were significantly lower during ICU stay, and aPTT ratio was more prolonged in the therapeutic group (p < 0.05). Conclusion Increasing the anticoagulation of severe COVID-19 patients to a therapeutic level might decrease thrombotic complications without increasing their bleeding risk.

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