- Pilot study of novel lab methodology and testing of platelet function in adolescent women with heavy menstrual bleeding. [Journal Article]
- PRPediatr Res 2018; 83(3):693-701
- BackgroundApproximately 40% of adolescent women experience heavy menstrual bleeding (HMB), and 10-62% of them have an underlying bleeding disorder (BD). Diagnosing a BD remains challenging because of...
BackgroundApproximately 40% of adolescent women experience heavy menstrual bleeding (HMB), and 10-62% of them have an underlying bleeding disorder (BD). Diagnosing a BD remains challenging because of limitations of available clinical platelet function assays. The aim of this study was to characterize platelet function in a population of adolescent women with HMB using small-volume whole-blood assays.MethodsAnticoagulated whole blood was used to assess platelet GPIIbIIIa activation, α-granule secretion, and aggregation in response to multiple agonists. Platelet adhesion on collagen or von Willebrand Factor (VWF) under static and shear flow was also assessed.ResultsFifteen participants with HMB were included in the study, of which eight were diagnosed with a clinically identifiable BD. Platelet activation was blunted in response to calcium ionophore in participants without a BD diagnosis compared with that in all other participants. Impaired GPIIbIIIa activation was observed in response to all GPCR agonists, except adenosine diphosphate (ADP), in participants with qualitative platelet disorders. Our assays detected platelet aggregation in the majority of participants with a BD in response to ADP, collagen-related peptide (CRP), thrombin receptor activator 6 (TRAP-6), or U46619. Platelet adhesion and aggregation on collagen and VWF was decreased for participants with VWD.ConclusionParticipants with and without BD exhibited aberrant platelet function in several assays in response to select agonists.
- A rare case of bleeding disorder: Glanzmann's thrombasthenia. [Case Reports]
- AAAnn Afr Med 2017 Oct-Dec; 16(4):196-198
- CONCLUSIONS: GT should always be considered as differential diagnosis while evaluating any case of bleeding disorder.
- Evaluation of platelet surface glycoproteins in patients with Glanzmann thrombasthenia: Association with bleeding symptoms. [Journal Article]
- IJIndian J Med Res 2017; 145(5):629-634
- CONCLUSIONS: Type I GT was found most common in our patients and with lowered mean CD41 expression in comparison with CD61. Type III GT patients had significantly lower numbers of severe bleeders, but the severity of bleeding did not vary significantly in type I and II GT patients.
- Von Willebrand's disease: case report and review of literature. [Case Reports]
- PAPan Afr Med J 2017; 27:147
- Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothel...
Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL). Von willebrand factor is a complex multimeric protein with two functions: it forms a bridge between the platelets and areas of vascular damage and it binds to and stabilizes factor VIII, which is necessary for the clotting cascade. By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA) the multimeric structure and collagen binding test and genanalysis allow diagnosing the different types of von. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of VWF. We report a case of infant in 27-month-old boy who had been referred due to haemorrhagic shock. His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to the symptoms, the child was on a normal diet and was thriving appropriately. The child presented one days before his admission trauma to the inner face of the lower lip that caused an external acute bleeding loss. The laboratory data showed unfortunately, the most severe form of Von Willebrand's Disease; Type 3. The management was based on erythrocyte and fresh-frozen plasma (FFP) transfusions with administration of factor VII with good evolution.
- Cardiovascular and Hemostatic Disorders: SOCE and Ca2+ Handling in Platelet Dysfunction. [Review]
- AEAdv Exp Med Biol 2017; 993:453-472
- Among the Ca2+ entry mechanisms in platelets, store-operated Ca2+ entry (SOCE) plays a prominent role as it is necessary to achieve full activation of platelet functions and replenish intracellular C...
Among the Ca2+ entry mechanisms in platelets, store-operated Ca2+ entry (SOCE) plays a prominent role as it is necessary to achieve full activation of platelet functions and replenish intracellular Ca2+ stores. In platelets, as in other non-excitable cells, SOCE has been reported to involve the activation of plasma membrane channels by the ER Ca2+ sensor STIM1. Despite electrophysiological studies are not possible in human platelets, indirect analyses have revealed that the Ca2+-permeable channels involve Orai1 and, most likely, TRPC1 subunits. A relevant role for the latter has not been found in mouse platelets. There is a body of evidence revealing a number of abnormalities in SOCE or in its molecular regulators that result in qualitative platelet disorders and, as a consequence, altered platelet responsiveness upon stimulation with multiple physiological agonists. Platelet SOCE abnormalities include STIM1 and Orai1 mutations. This chapter summarizes the current knowledge in this field, as well as the disorders associated to platelet SOCE dysfunction.
- Whole Blood Platelet Aggregometry. [Journal Article]
- MMMethods Mol Biol 2017; 1646:333-347
- Light transmittance aggregometry is the historical reference method for platelet function testing and continues to be used extensively. Whole blood impedance lumiaggregometry represents an updated me...
Light transmittance aggregometry is the historical reference method for platelet function testing and continues to be used extensively. Whole blood impedance lumiaggregometry represents an updated methodology that provides for simplified specimen management, an assay milieu that replicates in vivo platelet activation conditions, improved reproducibility, and near-patient testing. While the impedance-based whole blood aggregometer with luminescence channel is becoming the standard for platelet function testing using this methodology, at least three near-patient whole blood instruments are available, each employing its unique technology. We provide descriptions of whole blood lumiaggregometry and three near-patient systems. We include the principle of operation, materials, and stepwise example protocols and speculate on the importance of concordance among the platforms.
- Application of a strain rate gradient microfluidic device to von Willebrand's disease screening. [Journal Article]
- LCLab Chip 2017 07 25; 17(15):2595-2608
- Von Willebrand's disease (VWD) is the most common inherited bleeding disorder caused by either quantitative or qualitative defects of von Willebrand factor (VWF). Current tests for VWD require relati...
Von Willebrand's disease (VWD) is the most common inherited bleeding disorder caused by either quantitative or qualitative defects of von Willebrand factor (VWF). Current tests for VWD require relatively large blood volumes, have low throughput, are time-consuming, and do not incorporate the physiologically relevant effects of haemodynamic forces. We developed a microfluidic device incorporating micro-contractions that harnesses well-defined haemodynamic strain gradients to initiate platelet aggregation in citrated whole blood. The microchannel architecture has been specifically designed to allow for continuous real-time imaging of platelet aggregation dynamics. Subjects aged ≥18 years with previously diagnosed VWD or who presented for evaluation of a bleeding disorder, where the possible diagnosis included VWD, were tested. Samples were obtained for device characterization as well as for pathology-based testing. Platelet aggregation in the microfluidic device is independent of platelet amplification loops but dependent on low-level platelet activation, GPIb/IX/V and integrin αIIbβ3 engagement. Microfluidic output directly correlates with VWF antigen levels and is able to sensitively detect aggregation defects associated with VWD subtypes. Testing demonstrated a strong correlation with standard clinical laboratory-based tests. Head-to-head comparison with PFA100® demonstrated equivalent, if not improved, sensitivity for screening aggregation defects associated with VWD. This strain rate gradient microfluidic prototype has the potential to be a clinically useful, rapid and high throughput-screening tool for VWD as well as other strain-dependent platelet disorders. In addition, the microfluidic device represents a novel approach to examine the effects of high magnitude/short duration (ms) strain rate gradients on platelet function.
- Myeloid neoplasms with germ line RUNX1 mutation. [Review]
- IJInt J Hematol 2017; 106(2):183-188
- Familial platelet disorder with propensity to myeloid malignancies (FPD/AML) is an autosomal dominant disorder characterized by quantitative and/or qualitative platelet defects with a tendency to dev...
Familial platelet disorder with propensity to myeloid malignancies (FPD/AML) is an autosomal dominant disorder characterized by quantitative and/or qualitative platelet defects with a tendency to develop a variety of hematological malignancies. Heterozygous germ line mutations in the RUNX1 gene are responsible genetic events for FPD/AML. Notably, about half of individuals in the family with germ line mutations in RUNX1 develop overt hematological malignancies. The latency is also relatively long as an average age at diagnosis is more than 30 years. Similar to what is observed in sporadic hematological malignancies, acquired additional genetic events cooperate with inherited RUNX1 mutations to progress the overt malignant phase. Reflecting recent increased awareness of hematological malignancies with germ line mutations, FPD/AML was added in the revised WHO 2016 classification. In this review, we provide an update on FPD/AML with recent clinical and experimental findings.
- A case of autoimmune severe acquired von Willebrand syndrome (type 3-like). [Case Reports]
- TATransfus Apher Sci 2017; 56(3):431-433
- Von Willebrand disease (VWD) is the most common congenital bleeding disorder and is due to quantitative or qualitative defects of von Willebrand factor (VWF). Acquired defects of VWF, termed acquired...
Von Willebrand disease (VWD) is the most common congenital bleeding disorder and is due to quantitative or qualitative defects of von Willebrand factor (VWF). Acquired defects of VWF, termed acquired von Willebrand syndrome (AVWS), are due to a host of different mechanisms. Autoantibody-mediated AVWS may be associated with lymphoproliferative or immunological disorders, such as systemic lupus erythematosus (SLE). A large majority of AVWS cases are type 1 or type 2A-like and patients tend to have a mild to moderate bleeding tendency. We report a case of severe autoimmune AVWS in a woman with SLE who presented with clinical and laboratory features of type 3 VWD (undetectable VWF antigen, ristocetin cofactor activity, and VWF multimers). A mixing study demonstrated an inhibitor to VWF (6BU/mL). Her bleeds were managed with antifibrinolytics, recombinant activated factor VII, and activated prothrombin complex concentrate. She was initially treated with steroids and intravenous immunoglobulin therapy. However, her bleeding symptoms continued until she was treated with rituximab, and her VWF parameters normalized. She relapsed two years later due to non-compliance with her immunosuppressive medications and expired another two years later secondary to complications of sepsis and uremic pericarditis. This case emphasizes the importance of aggressive initial therapy of SLE to reduce secondary complications, frequent patient monitoring, and continued treatment of the underlying autoimmune disorder in patients with AVWS.
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- The role of thromboelastometry in the assessment and treatment of coagulopathy in liver transplant patients. [Journal Article]
- EEinstein (Sao Paulo) 2017 Apr-Jun; 15(2):243-246
- Perioperative monitoring of coagulation is vital to assess bleeding risks, diagnose deficiencies associated with hemorrhage, and guide hemostatic therapy in major surgical procedures, such as liver t...
Perioperative monitoring of coagulation is vital to assess bleeding risks, diagnose deficiencies associated with hemorrhage, and guide hemostatic therapy in major surgical procedures, such as liver transplantation. Routine static tests demand long turnaround time and do not assess platelet function; they are determined on plasma at a standard temperature of 37°C; hence these tests are ill-suited for intraoperative use. In contrast, methods which evaluate the viscoelastic properties of whole blood, such as thromboelastogram and rotational thromboelastometry, provide rapid qualitative coagulation assessment and appropriate guidance for transfusion therapy. These are promising tools for the assessment and treatment of hyper- and hypocoagulable states associated with bleeding in liver transplantation. When combined with traditional tests and objective assessment of the surgical field, this information provides ideal guidance for transfusion strategies, with potential improvement of patient outcomes. RESUMO A monitorização perioperatória da coagulação é fundamental para estimar o risco de sangramento, diagnosticar deficiências causadoras de hemorragia e guiar terapias hemostáticas durante procedimentos cirúrgicos de grande porte, como o transplante hepático. Os testes estáticos, comumente usados na prática clínica, são insatisfatórios no intraoperatório, pois demandam tempo e não avaliam a função plaquetária; são determinados no plasma e realizados em temperatura padrão de 37°C. Os métodos que avaliam as propriedades viscoelásticas do sangue total, como o tromboelastograma e a tromboelastometria rotacional, podem suprir as deficiências dos testes estáticos tradicionais, uma vez que permitem avaliar a coagulação de forma rápida e qualitativa, guiando a terapia transfusional de forma adequada. A tromboelastometria rotacional mostrou-se promissora na avaliação e no tratamento de estados de hipercoagulação e hipocoagulação, associados a sangramento no transplante hepático. Estas informações, combinadas com os testes tradicionais e uma avaliação objetiva do campo cirúrgico, promovem um cenário ótimo para guiar as estratégias transfusionais e potencialmente melhorar o desfecho destes pacientes.