Combination Of Thrombocytopenia Research Articles

Scoring systems for prediction of malaria and dengue fever in non-endemic areas among travellers arriving from tropical and subtropical areas

BackgroundFever is a common symptom among travellers returning from tropical/subtropical areas to Europe, and promptly distinguishing severe illnesses from self-limiting febrile syndromes is important but can be challenging due to...

Guidelines on: COVID-19 Vaccine Induced Thrombosis, Bleeding, and Thrombocytopenia

After widespread vaccination with COVID-19 vaccines, there have been worldwide reports on thrombosis, bleeding, and thrombocytopenia. Recently, a rare syndrome with a high mortality rate consisting of an unusual combination of thrombocytopenia and thrombosis, in particular cerebral venous sinus thrombosis, which clinically resembles heparin-induced thrombocytopenia, was reported following vaccination. Different statements and recommendations were developed regarding the definition, diagnosis, and treatment of these rare complications. We present here a protocol with recommendations, based on current evidence.

An unusual non-resolving community-acquired pneumonia

We present the case of a 61-year-old male that was admitted to our Unit of Pulmonology for a suspected community-acquired pneumonia (CAP) with acute hypoxemic respiratory failure. However, despite many courses of empiric wide spectrum antibiotic treatment, the respiratory failure persisted and new bilateral migratory pulmonary opacities and serosal effusions appeared. The most common causes of non-resolving CAP were excluded and the combination of thrombocytopenia, autoimmune hemolysis, pleural and pericardial effusions in a patient with antinuclear antibodies ANA at a titer of 1:160 is diagnostic for systemic lupus erythematosus (SLE)

HIT-Heparin Induced Thrombocytopenia Simulation Case.

The aim of this simulation is to educate emergency medicine interns, residents and advanced providers on the recognition, diagnosis, and management of heparin-induced thrombocytopenia (HIT). Communication, teamwork, and crisis resource management are incorporated into the case. Heparin-induced thrombocytopenia is a life-threatening complication of heparin exposure (eg, unfractionated heparin, low molecular weight [LMW] heparin) that occurs in a small percentage of patients exposed.1 It results in a consumptive coagulopathy in which the clotting cascade is inappropriately activated, leading to a low platelet count yet hypercoagulable state. HIT is associated with mortality rates of 20-30%, with a similar percentage of patients becoming subsequently disabled due to severe complications including limb amputation, multi-system organ failure, stroke or other causes of morbidity.2 Heparin-induced thrombocytopenia often presents 5 to 15 days after starting heparin treatment, and with more outpatients being treated with heparin products, it is likely that a first-line provider, such as an emergency medicine physician, would be the first clinician to encounter these patients. The combination of thrombocytopenia and hypercoagulability, along with the rarity of the disease, can make this difficult to diagnose and puts the first line clinician at risk for mismanagement. It is important to be familiar with the signs and symptoms of HIT and to refrain from starting heparin or platelets upon discovery of thrombosis or thrombocytopenia because it will lead to severe and rapid patient deterioration. Therefore, the ability to quickly recognize and treat this condition properly is an essential skill for emergency medicine physicians. Our goal is to create a simulated case that familiarizes emergency providers to this condition so they can be comfortable diagnosing and managing it in a real clinical scenario. After completing this simulated case, participants will be able to: Obtain a detailed history that includes recent medications, medical, surgical, and social history to evaluate for HIT risk factors.Perform an adequate neurovascular exam including evaluation of motor function, sensation, skin color, pulses, and capillary refill.Order appropriate laboratory testing and imaging for diagnosis of thrombocytopenia and arterial occlusion, including bed side doppler or ultrasound.Discuss and recognize the symptoms of HIT and the contraindications of platelet and heparin administration in the emergency department.Avoid administration of heparin in the emergency department setting and recognize that platelets may worsen thrombus formation and lead to limb amputation.2Select appropriate medications for treatment and determine appropriate disposition for a patient presenting with HIT.Demonstrate interpersonal communication with patient and family.Recognize that HIT with thrombosis is a potential complication in hospitalized patients and outpatient settings and is associated with high mortality rates. This is a high-fidelity simulation case that allows participants to diagnose and treat HIT in a safe environment. The case is followed by a debriefing and small group discussion to review patient care skills, medical knowledge, interpersonal communication, and practice-based learning and improvement. The educational content and efficacy were evaluated by oral feedback and a debriefing session immediately after completion of the simulation. Participants were provided with an evaluation at the completion of the debriefing session to provide qualitative feedback on the simulation case. A quality Likert Scale was used for the evaluation. Post-simulation feedback resulted in positive reception, and learners found it useful to run through a high-risk case potentially seen in the emergency department. Out of the 21 participants, 14 responded to the evaluation. Feedback was overwhelmingly positive with the majority rating the simulation as excellent or good.Discussion: The simulation improved awareness of the symptoms of HIT and contraindications of immediate platelet and/or heparin initiation upon vessel occlusion and thrombocytopenia discovery.Topics: Heparin-induced thrombocytopenia, pain control, resuscitation efforts, coagulation disorders, history taking, undifferentiated patient, arterial occlusion, hematology, emergency medicine simulation.

Особенности вязко-эластических свойств сгустка крови и проявления геморрагического синдрома при тромбоцитопении у онкогематологических больных

Введение. Тромбоцитопения является частым осложнением онкогематологических заболеваний, которое провоцирует развитие геморрагического синдрома. Уровень тромбоцитов в периферической крови, являющийся пороговым для переливания концентрата тромбоцитов (КТ), окончательно не установлен. Применение тромбоэластографии (ТЭГ) при тромбоцитопениях у онкогематологических больных может повысить прогностические возможности определения риска кровотечений. Цель исследования: оценить вязко-эластические свой ства сгустка крови при тромбоцитопении менее 50×109/л и их взаимосвязь с проявлениями геморрагического синдрома у онкогематологических больных. Материалы и методы. В исследование включено 84 пациента с гемобластозами и тромбоцитопенией менее 50×109/л, 54 (64%) мужчины и 30 (36%) женщин, медиана возраста — 54 года. В зависимости от уровня тромбоцитов в периферической крови пациентов разделили на 2 группы: группа 1 — 44 пациента с числом тромбоцитов от 25 до 50×109/л, группа 2 — 40 больных с содержанием тромбоцитов менее 25×109/л. Исследовали показатели периферической крови, коагулограммы и ТЭГ. Степень тяжести кровотечений оценивали по шкале проявлений геморрагического синдрома (ВОЗ) и по шкале оценки побочных явлений Национального института рака (США). Результаты. Гипокоагуляция по ТЭГ в группе 1 выявлена в 46% случаев, в группе 2 — в 75%. Значимые межгрупповые различия показателей ТЭГ получены только в отношении максимальной амплитуды. Геморрагический синдром в группе 1 диагностирован у 6 (13%) пациентов, в группе 2 — у 14 (35%). Однако предиктивная роль влияния количества тромбоцитов на частоту развития геморрагического синдрома не установлена (β = 0,016; p = 0,92). Сочетание тромбоцитопении и гипокоагуляции по ТЭГ проявлялось в виде геморрагического синдрома в 3,3 раза чаще, чем без гипокоагуляции (RR = 3,3; 95% ДИ = 1,20–9,05). В ряде случаев основанная на результатах ТЭГ трансфузионная тактика позволила избежать переливания КТ при инвазивных манипуляциях у больных с тромбоцитопенией менее 25 × 109 / л. Заключение. Глубина тромбоцитопении не является надежным предиктором геморрагического синдрома. Применение ТЭГ у пациентов с тромбоцитопенией позволяет оптимизировать трансфузионную тактику, избежав ненужных переливаний КТ. Сочетание тяжелой тромбоцитопении с гипокоагуляцией по данным ТЭГ служит показанием для профилактических трансфузий КТ. Background. Thrombocytopenia is a frequent complication of hemoblastosis that causes hemorrhagic syndrome. The threshold of peripheral blood platelet count for transfusion of platelet concentrate is discussed. Thromboelastography (TEG) can be considered as additional prognostic method for bleeding risk assessment in thrombocytopenic patients with leukemia. Objectives: to study changes in the viscoelastic properties of blood clot in hemoblastosis patients with thrombocytopenia less than 50×109/L and their relationship with the manifestations of hemorrhagic syndrome. Patients/ Methods. The study included 84 hemoblastosis patients — 54 (64%) men и 30 (36%) women with thrombocytopenia less than 50 × 109/L, median age — 54 years. All patients are divided into 2 groups according to the platelet count: Group 1 — 25–50×109/L, Group 2 — less than 25×109/L. Peri pheral blood counts, TEG and coagulogram parameters were evaluated in both groups. Manifestations of hemorrhagic syndrome were assessed according to the WHO bleeding scale and Common terminology criteria for adverse events of the National Cancer Institute (USA). Results. Hypocoagulation according TEG in Group 1 was found in 46% of cases, in Group 2 — in 75%. Significant intergroup differences in TEG parameters were obtained only in maximum amplitude. Hemorrhagic syndrome in Group 1 diagnosed in 6 (14%) patients, in Group 2 — in 14 (35%). There was no dependence of hemorrhagic syndrome frequency on the severity of thrombocytopenia (β = 0.016; p = 0.92). The combination of thrombocytopenia and hypocoagulation according TEG manifested as a hemorrhagic syndrome 3.3 times more often than without hypocoagulation (RR = 3.3; 95% CI = 1.20–9.05). In some cases, TEG-based transfusion tactics allowed to avoid unnecessary platelet concentrate transfusion during invasive procedures in patients with thrombocytopenia less than 25 × 109/L. Conclusions. Severity of platelet depletion is not accuracy predictor for hemorrhagic events. Use of TEG in patients with thrombocytopenia allows to optimize the transfusion tactics and to avoid unnecessary platelet concentrate transfusions. The combination of severe thrombocytopenia with hypocoagulation according TEG serves as indication for prophylactic platelet concentrate transfusion.

Mechanisms and management of coagulopathy in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a subtype of leukemia which is associated with unique and distinctive coagulopathy. In the absence of treatment it is rapidly fatal and even after initiation of therapy the major cause of early mortality is related to hemorrhagic complications. The coagulopathy can be exacerbated with the start of treatment. In the absence of early hemorrhage related deaths the probability of cure exceeds 90% in low and intermediate risk patients and 80% even in high risk patients, highlighting the importance of understanding the pathophysiology of this complication and instituting prompt and appropriate management strategies. The coagulopathy in APL is complex and results from a combination of thrombocytopenia, disseminated intravascular coagulation and hyperfibronlysis. Recently the effect of all-trans retinioc acid (ATRA) induced ETosis on exacerbating coagulopathy in the first few days after starting therapy with this agent raises the potential for potentially novel strategies to reduce the risk of hemorrhage. Currently management is mainly related to rapid initiation of therapy with ATRA along with appropriate and adequate replacement of blood products to correct the coagulopathy. There is limited role for the use of low dose anti-coagulants and anti-fibrinolytic agents in the initial management of this disease. There is limited data on the use of rFVIIa or the use of global tests of hemostasis in the management of this condition.

Cytomegalovirus With Cirrhosis and Clopidogrel: A Cocktail for Recurrent Lower Gastrointestinal Bleeding

In an immunosuppressed patient, Cytomegalovirus (CMV) infection in the colon has been reported to manifest in a variety of presentations. We highlight a case with recurrent, significant hematochezia in a patient with cirrhosis and coronary artery disease (CAD) on dual antiplatelet therapy. A 62-year-old man with history of end stage renal disease, AIDS on highly active anti-retroviral therapy (HAART), CAD on aspirin and clopidogrel and compensated alcoholic cirrhosis presented with hematochezia for two weeks. He denied systemic symptoms including fever or significant weight loss. Vitals were stable and labs were remarkable for pancytopenia: Hemoglobin 6.3 gms/dL, Platelets 70 K/ul, WBC 2.0 K/ul. Liver function tests and coagulation markers were normal while CD4 count was 212/mm3. Colonoscopy showed three short stenotic, ulcerated segments in transverse and ascending colon with active oozing and normal intervening mucosa (Figure 1, A-D). Biopsies from the ulcers were non-diagnostic with no neoplastic cells and negative CMV stain. Aspirin and clopidogrel were continued due to perceived risk for vascular events and cessation of lower GI bleeding. The patient was discharged with a hemoglobin of 10.1 gms/dL, after emphasizing the importance of compliance with HAART. Three weeks after the first admission, the patient presented again with hematochezia and drop in hemoglobin to 5.8 gms/dl. Repeat colonoscopy revealed healing stenotic segments at the same locations (Fig 2 A-C). Biopsies from the lesions showed CMV positive cells with background granulation tissue. Hematochezia resolved with cessation of Plavix and the patient was discharged only on aspirin with no further recurrence. Compliance with HAART therapy resulted in objective improvement of the colonic lesions, without need for targeted anti-CMV therapy. Despite improvement in the colonic ulcers, his hematochezia appeared to have been precipitated by the combination of thrombocytopenia from cirrhosis and dual anti-platelet therapy. Discontinuation of the Plavix resulted in successful cessation of bleeding. CMV should be considered in the work up of colon ulcers and strictures in an immunosuppressed patient. While CMV colitis can present with hematochezia in immunocompromised patients, additional factors including thrombocytopenia and anti-platelet therapy may play a role in patients with recurrent, persistent bleeding, especially when there is evidence of improvement in the CMV infection.Figure: (A-D)- multiple colon short stenotic segment with ulcers (Index colonoscopy).Figure: (A-C)- Healing colon strictures with mild erythema on colonoscopy.

The history and accomplishments of the ICGG Gaucher registry.

The history and accomplishments of the ICGG Gaucher registry.

Late-onset bolus intravenous beta-lactam antibiotic adverse reaction: Short-lived symptoms during drug administration and associated laboratory abnormalities

In the 1970s, there were 2 reports of a late-onset adverse reaction during bolus infusions of benzyl penicillin, characterized by short-lived symptoms, most commonly abdominal pain. The mechanism is not known. We set out to further characterize this reaction. We conducted a prospective observational study of all adult patients receiving bolus intravenous (IV) beta-lactam antibiotics under the care of our Outpatient IV Antibiotic Service from 1 August 2007 to 31 January 2010, focusing on those who developed infusion-related symptoms. During the 30-month study, 11 of the 163 patients (7%) treated with bolus IV beta-lactam antibiotics developed a late-onset infusion-related adverse reaction. Six of 30 patients (20%) treated with benzyl penicillin developed this adverse reaction compared to 5 of 133 (4%) treated with any other beta-lactam antibiotic (p = 0.006). The median duration of beta-lactam antibiotic before reaction onset was 25 days. Abdominal pain occurred in 9 patients (82%), fever in 3 (27%), and rash in 5 (45%). Seven patients (64%) developed a combination of thrombocytopenia, neutropenia, and/or lymphopenia and 6 (55%), elevated liver enzymes. This adverse reaction, occurring late during prolonged IV bolus beta-lactam treatment, is most often characterized by short-lived abdominal pain occurring at the time of infusion and is more common in patients receiving benzyl penicillin. It is frequently associated with cytopenias and elevated liver enzymes. It may have both immunological and non-immunological mechanisms.

Castleman-Kojima Disease (TAFRO Syndrome) : A Novel Systemic Inflammatory Disease Characterized by a Constellation of Symptoms, Namely, Thrombocytopenia, Ascites (Anasarca), Microcytic Anemia, Myelofibrosis, Renal Dysfunction, and Organomegaly : A Status Report and Summary of Fukushima (6 June, 2012) and Nagoya Meetings (22 September, 2012)

Recently, a unique clinicopathologic variant of multicentric Castleman's disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, microcytic anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5 cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. [J Clin Exp Hematop 53(1): 57-61, 2013].

Applications of the international scoring system for Disseminated Intravascular Coagulopathy (DIC) and its interaction with Sequential Organ Failure Assessment Score (SOFA) in prediction of prognosis and final outcome in ICU

IntroductionDisseminated Intravascular Coagulopathy (DIC) is a consumptive syndrome that is characterized by simultaneous widespread microvascular thrombosis and profuse bleeding from various sites. It is described as the combination of thrombocytopenia, decreased coagulation factors V and X causing prolonged prothrombin time, together with decreased fibrinogen and increased D-dimer levels. Objectives(1) To investigate the relation between DIC and increased mortality, (2) to explain the impact of the changes that occur in ISTH score for DIC in critically ill patients, (3) to determine the prognostic role of interacting DIC and SOFA scores in critically ill patients and their predictive capability when combined together than either score alone. DesignA prospective, comparative, cohort, non-controlled, single center study from July 2011 to January 2012. SettingIntensive care unit at Critical Care Department in Kasr-Alainy Hospital of Cairo University. PatientsFifty critically ill patients with APACHE II score ⩾25, not including those with disseminated malignancies, chronic liver failure, renal failure or chronic haematological disorders. MeasurementsFor all included patients with APACHE II score ⩾25 on admission, DIC and SOFA scores were calculated at baseline (on admission) and subsequently thereafter every 48h until ICU discharge or death or up to a total of 28days. Clinical outcome (duration of stay in the ICU, need for mechanical ventilation, need for inotropic/vasopressor support, need for haemodialysis, and final outcome of survival/mortality rates) were recorded. ResultsThrough follow up of DIC score trend in both groups (survivors and non-survivors); increasing value was associated with poor prognosis (96.8% of non-survivors had DIC score value on admission lower than that before death), while decreasing or constant value was associated with better prognosis (94.4% of non-survivors had DIC score value on admission higher than or equal to that before discharge). There was a significant correlation between combined DIC and SOFA scores together with mortality and final outcome in ICU (P value was 0.002 at day 4 and 0.012 on discharge or at death). ConclusionA significant correlation exists between SOFA and DIC scores together in critically ill patients with APACHE II score ⩾25 as regards MODS and mortality. The combination of DIC and SOFA scores highly improves the prognostic performance of either score alone. It's recommended to combine these scores together for better mortality prediction.

Thrombotic microangiopathy in sickle cell disease crisis

Thrombotic microangiopathy (TMA) in patients with sickle cell disease (SCD) is a rare complication. These patients manifest microangiopathic hemolytic anemia (MAHA) with laboratory evidence of hemolytic anemia, schistocytosis, and thrombocytopenia. This is the first report of the syndrome in a group of these patients. A retrospective chart analysis of 10 consecutively diagnosed patients in SCD crisis who were referred for therapeutic plasma exchange (TPE) after developing MAHA was done. Patients had chest pain, respiratory distress, fever, pulmonary infiltrates, jaundice, and neurological dysfunction with abnormal liver function and coagulation tests. MAHA was diagnosed after a median hospital stay of 5 days. Nine patients recovered completely following TPE with fluid replacement by fresh frozen plasma with or without cryo-poor plasma. Incomplete response to TPE in one case was due to the development of fresh complications. During a median follow-up period of 77 months, there was one recurrent episode and one death in SCD crisis but without evidence of MAHA. TMA is not a very rare complication among Bahraini SCD patients in crisis. Characteristic features of this disorder are acute chest syndrome, organ failure, leuco-erythroblastosis, and a combination of thrombocytopenia, LDH level >1,000 U/l, and schistocytes in blood smears. Management with TPE usually leads to complete recovery with little chance of short-term recurrence. Multiple pathogenetic mechanisms leading to increased von Willebrand factor and its multimers may form the basis of this syndrome.

Letter to the editor Cyclophosphamide-rescued plasmapheresis-unresponsive secondary thrombotic thrombocytopenic purpura caused by Sjögren’s syndrome

Letter to the editor Cyclophosphamide-rescued plasmapheresis-unresponsive secondary thrombotic thrombocytopenic purpura caused by Sjögren’s syndrome

Acute Dengue Fever with Computed Tomography (CT) Correlation

A 23-year-old female presented to the emergency department with vomiting and abdominal pain. She had traveled home to Canada the previous day from Indonesia and Thailand. Her symptoms had started 5 days previously in Bangkok with malaise and fever. On clinical examination she looked ill with a low-grade fever of 37.3°C. Cardiovascular, respiratory, and neurological examinations were normal. On examination, her abdomen was extremely tender with guarding of the right upper quadrant. A diffuse purpuric erythematous rash was noted over her extremities and trunk (Figure 1). Figure 1. Purpuric rash on both legs. This figure appears in color at www.ajtmh.org. Laboratory tests revealed a low platelet level at 34 with raised liver transaminases: aspartate aminotransferase 244 and alanine aminotransferase 111. Malaria smear was negative. Chest radiograph at initial presentation was negative but within 24 hours after the highest fever at 39.4°C showed moderate bilateral pleural effusions (Figure 2). Figure 2. (A) Chest radiograph at initial presentation and (B) after 24 hours showing bilateral pleural effusions (white arrows). Computed tomography (CT) of the abdomen showed a moderate amount of low-attenuation free fluid in the abdomen and pelvis with periportal edema and pericholecystic fluid (Figure 3). Figure 3. Computed tomography (CT) of the abdomen including the lung bases (A) showed bilateral pleural effusions without evidence of pulmonary edema on lung windows (B). Moderate amount of free fluid seen in the upper abdomen (C, D) with periportal edema (white ... The combination of thrombocytopenia and imaging findings consistent with plasma leakage are suggestive of dengue hemorrhagic fever1; later confirmed on serology with both single IgG and IgM positive results. Imaging in assessment of fluid in multiple body compartments becomes detectable at the time of the immune response and typically at the time of disappearance of fever and is well demonstrated on both CT and ultrasound examinations.2

Monosomy 21q22.11‐q22.13 presenting as a Fanconi anemia phenotype

We report on a 5-year-old Caucasian female with multiple anomalies whose deletion, 46,XX,del(21)(q22.11q22.13), was determined by a 105K oligonucleotide-based microarray. This case is a unique deletion that mimicked Fanconi anemia (combination of thrombocytopenia, thumb anomalies, congenital heart defects, borderline small head circumference, strabismus, hydronephrosis, and significant developmental delay) but testing for Fanconi anemia was negative, as was testing for a wide array of genetic/metabolic conditions. Microarray testing done at 5 months failed to demonstrate the interstitial deletion that was found on a newer generation microarray test performed after 3 years of age. When compared to other reported cases of partial monosomy 21q, the unique features of this case include: (1) cleft palate, although high palate is reported in other cases; (2) neonatal thrombocytopenia requiring platelet transfusion; (3) a platelet function defect, reported previously as platelet storage pool defect as part of a familial platelet disorder; and (4) an immune function defect. Similar to other reported patients with terminal 21q deletion, this child had significant developmental delay, and feeding and growth problems. This case also highlights the ability for newer technology microarrays to identify small interstitial deletions previously missed by an earlier version microarray. The advances in the microarray technologies are allowing us to better define new phenotypes and leading to the identification of a diagnosis for many patients who have been previously undiagnosed. Review of the genes involved in these novel deletions allows the caring physician to design surveillance strategies that are custom-designed for these unique patients.

Incidence of Bleeding Following Invasive Procedures in Patients With Thrombocytopenia and Advanced Liver Disease

Patients with advanced liver disease often undergo invasive procedures, so the combination of thrombocytopenia, coagulopathy, and bleeding should be carefully assessed. We evaluated the prevalence of thrombocytopenia in a series of patients with liver cirrhosis who were being evaluated for orthotopic liver transplantation (OLT) and determined the number of invasive procedures and procedure-related incidences of bleeding in patients with thrombocytopenia. We studied 121 consecutive patients who were being evaluated for OLT. Thrombocytopenia was defined as a platelet count <150,000/μL and severe thrombocytopenia as a platelet count <75,000/μL. The presence of significant coagulopathy was defined as an international normalized ratio >1.5. Invasive procedures and incidences of procedure-related bleeding were recorded for each patient. The prevalence of thrombocytopenia and severe thrombocytopenia were 84% and 51%, respectively. Among the 102 thrombocytopenic patients, 50 (49%) underwent an invasive procedure (32 with severe thrombocytopenia; 64%). Bleeding occurred in 10 of the patients who underwent an invasive procedure (20%). Among the 50 patients who underwent invasive procedure, 32 had severe thrombocytopenia and 18 had moderate thrombocytopenia. Bleeding occurred in 10 of the 32 patients (31%) with severe thrombocytopenia and in none of those with moderate thrombocytopenia. There was no difference in prevalence of significant coagulopathy between patients with severe thrombocytopenia who underwent invasive procedure and bled (3/10; 30%) and those who did not bleed (10/22; 45%). Thrombocytopenia has a high prevalence among patients with advanced liver disease. Bleeding related to invasive procedures occurs most frequently in patients with severe thrombocytopenia, whereas significant coagulopathy does not seem to be associated with bleeding.

What Level of Platelet Count and Symptoms Trigger Referral of Patients with Thrombocytopenia from Primary Care Physicians to Hematologists?

Introduction: Primary care physicians are typically the first physicians who see patients with thrombocytopenia. There are currently no data to document which patients who present with isolated thrombocytopenia or immune thrombocytopenic purpura (ITP) are referred to hematologists. The published ASH Practice Guideline on ITP (Blood 1996; 88:3) does not address the issue of referral to a hematologist; the British Committee for Standards in Haematology Guideline on ITP (Brit J Haematol 2003; 120:574) only recommends referral of children with severe chronic ITP. The goal of this study was to determine the level of thrombocytopenia or the combination of thrombocytopenia and bleeding symptoms that prompt family physicians to send patients to hematologists for further evaluation and management. Our a priori assumption was that this level would be less than or equal to 30,000/μL, regardless of bleeding symptoms.Methods: A survey was conducted in collaboration with the Oklahoma Physicians Resource-Research Network (OKPRN). The mission of the OKPRN is to provide community physicians with access to information and research opportunities to enhance their practices and to generate new knowledge through practice-based research. OKPRN family physicians (N=127) were asked to complete a short eight-item questionnaire consisting of five patient vignettes with varying degrees of thrombocytopenia and bleeding symptoms. For each vignette, the physician was to decide when or if he/she would send the patient to a hematologist for further management using a four point likert scale. The response categories were ‘very unlikely’, ‘unlikely’, ‘likely’, and ‘very likely’. The response scale was dichotomized (unlikely vs likely) to graphically display results across all five patient vignettes.Results: There was a 66% (84/127) response rate. Fifty-one percent (43/84) of the responders had been practicing family medicine between 6–20 years, 37% (31/84) for more than 20 years, and 12% (10/84) had been practicing between 1–5 years. Sixty-one percent (51/84) responded that there was a hematologist that they routinely called on the phone for advice and/or sent referrals, and 81% (68/84) practiced within 50 miles of a hematologist. Figure 1 shows as a patient's thrombocytopenia became more severe, the likelihood of referral to a hematologist increased. Seventy-five percent of the respondents surveyed were ‘likely’ to send a patient with moderate thrombocytopenia (platelet count 30,000/μL) without bleeding symptoms to a hematologist. The likelihood of referral increased to 85% when the moderate thrombocytopenia was associated with mild bleeding symptoms, and over 90% when a patient presented with severe thrombocytopenia (platelet count 10,000/μL) and bleeding symptoms. [Display omitted] Conclusion: Results from the OKPRN survey documented that patients with isolated thrombocytopenia and a platelet count of 80,000/μL would infrequently be referred to a hematologist while patients with platelet counts of ≤30,000/μL would almost always be referred, especially if there were bleeding symptoms. Results from this survey validate assumptions that ITP patients with moderate to severe thrombocytopenia are managed by hematologists, not primary care physicians. These data are important to define the scope of practice of hematology.

Fieber, Nasenbluten und myalgiforme abdominale Schmerzen

A 38 year old patient presented with fever, myalgic abdominal pain, nose bleeding and acute renal failure since five days. A combination of thrombocytopenia, proteinuria, elevated CrP and creatinin is common in hemorrhagic fever with renal syndrome (HFRS) due to Hantavirus infection. The benigne form is called Nephropathia epidemica. Dialysis is infrequently required by patients with the Puumala virus. Other infection (e.g. malaria, leptospirosis, yellow fever) and systemic diseases (e.g. collagenosis or vasculitis) are considered.

Clinical features and pitfalls in the laboratory diagnosis of dengue in travellers

BackgroundSeveral enzyme-linked immunosorbent assay (ELISA)-kits are commercially available for the rapid diagnosis of dengue infection, and have demonstrated good sensitivity and specificity in paired serum samples. In practice, however, often only one blood sample is available from febrile travellers returning from dengue endemic areas.MethodsTo evaluate the diagnostic value of positive dengue antibody-titres performed by a standard ELISA (PanBio IgM- and IgG-ELISA) in single serum samples (regarded as "probable infection"), 127 positive samples were further analyzed using envelope/membrane IgM-, and nonstructural protein 1 IgM- and IgG-ELISAs, immunofluorescence assays, and real-time reverse transcription polymerase chain reaction assays (RT-PCR). A combination of the test-results served as the diagnostic "gold standard". A total of 1,035 febrile travellers returning from dengue-endemic countries with negative dengue-serology and RT-PCR served as controls to compare clinical and haematological features.ResultsOverall, only 64 (positive predictive value = 50%) of the probable cases were confirmed by additional analysis and 54 (42.5%) were confirmed to be "false-positive". Rash was the only clinical feature significantly associated with confirmed dengue fever. The combination of thrombocytopenia and leucopenia was present in 40.4% of confirmed and in 6.1% of false-positive cases. Thus, the positive predictive value for the combination of positive PanBio-ELISA plus the two haematological features was 90.5%.ConclusionThe examination of paired serum samples is considered the most reliable serodiagnostic procedure for dengue. However, if only one blood sample is available, a single positive ELISA-result carries a high rate of false-positivity and should be confirmed using a second and more specific diagnostic technique. In the absence of further testing, platelet and white blood cell counts are helpful for the correct interpretation.

Fever in the returning traveller.

Fever is a common reason for acute hospital admission for tropical illness in UK referral units. A sensible working diagnosis can usually be formulated from a careful history and examination and initial simple investigations. The history should include details of exactly where the patient has been, what conditions he or she was living in, and the exact dates of arrival and departure. The quality of pre-travel advice and vaccinations, adherence to chemoprophylaxis against malaria, avoidance of insect bites and general behaviour abroad (including sexual history) are also important. Localizing features of the illness should be sought on examination. Maintain a high index of suspicion for underlying HIV. The most important illness to consider and exclude is malaria (about 40% of cases), and most of the remainder have cosmopolitan viral infections or imported infections such as an arbovirus (dengue), enteric fever or viral hepatitis. Rarer causes are usually evident from the history and examination, which presupposes a good knowledge of geographical medicine. Initial investigations should include adequate malaria films (supplemented by quick antigen detection tests in many laboratories) and blood count, repeated as necessary, blood, urine and faecal cultures, serum biochemistry, chest radiography and other imaging (e.g. liver ultrasonography) as indicated. In patients in whom malaria is suspected despite negative films, the combination of thrombocytopenia and splenomegaly is supportive but not diagnostic of malaria.