Rare bleeding disorders: Advances in management.

Inherited factor coagulation deficiencies and vascular bleeding disorders, associated with bleeding of various severity, are often classified as rare bleeding disorders (RBDs). These include inherited fibrinogen disorders, inherited platelet function disorders (IPFD) and hereditary haemorrhagic telangiectasia (HHT). In the last decades, there have been large increases in knowledge on the epidemiology, genetics, physiopathology, clinical features, and diagnosis of RBDs, but improvements in management have been more limited and remain challenging. The treatment mainstay of RBDs is based only on replacement of a few available coagulation factor concentrates or cryoprecipitates. There is growing interest in therapeutic agents that enhance coagulation or inhibiting anticoagulant pathways in RBDs. In severe IPFD, the optimal platelet transfusion strategy is not yet established. Moreover, data is scarce on the effectiveness and safety of desmopressin and/or antifibrinolytic drugs often used for milder IPFD treatment. The best fibrinogen replacement strategy (prophylaxis vs. on demand) in afibrinogenemia is still debated. Similarly, the optimal trough fibrinogen target level for treatment of acute bleeding, and the role of fibrinogen replacement during pregnancy in mild hypofibrinogenemia and dysfibrinogenemia, have not been properly evaluated. The therapeutic arsenal in HHT includes antifibrinolytics and a series of antiangiogenic agents whose potential efficacy has been tested in small studies or are under investigation for treatment of bleeding. However, there is need to address several issues, including the optimal dosing strategies, the potential emergent toxicity of longer-term use, and the impact of systemic antiangiogenic treatment on visceral arteriovenous malformations.

Investigation of the role of von Willebrand factor in shear-induced platelet activation and functional alteration under high non-physiological shear stress.

BACKGROUND: von Willebrand factor (vWF) plays a crucial role in physiological hemostasis through platelet and subendothelial collagen adhesion. However, its role in shear-induced platelet activation and functional alteration under non-physiological conditions common to blood-contacting medical devices (BCMDs) is not well investigated. METHODS: Fresh healthy human blood was treated with an anti-vWF antibody to block vWF-GPIbα interaction. Untreated blood was used as a control. They were exposed to three levels of non-physiological shear stress (NPSS) (75, 125, and 175 Pa) through a shearing device with an exposure time of 0.5 s to mimic typical shear conditions in BCMDs. Flow cytometric assays were used to measure the expression levels of PAC-1 and P-Selectin and platelet aggregates for platelet activation and the expression levels of GPIbα, GPIIb/IIIa, and GPVI for receptor shedding. Collagen/ristocetin-induced platelet aggregation capacity was characterized by aggregometry. RESULTS: The levels of platelet activation and aggregates increased with increasing NPSS in the untreated blood. More receptors were lost with increasing NPSS, resulting in a decreased capacity of collagen/ristocetin-induced platelet aggregation. In contrast, the increase in platelet activation and aggregates after exposure to NPSS, even at the highest level of NPSS, was significantly lower in treated blood. Nevertheless, there was no notable difference in receptor shedding, especially for GPIIb/IIIa and GPVI, between the two blood groups at the same level of NPSS. The block of vWF exacerbated the decreased capacity of collagen/ristocetin-induced platelet aggregation. CONCLUSIONS: High NPSS activates platelets mainly by enhancing the vWF-GPIbα interaction. Platelet activation and receptor shedding induced by high NPSS likely occur through different pathways.

An overview of qualitative and quantitative platelet abnormalities in schistosomiasis.

Schistosomiasis is a neglected tropical disease referring to the infection with blood parasitic trematodes of the genus Schistosoma. It impacts millions of people worldwide, primarily in low-to-middle-income countries. Patients infected with schistosomiasis often exhibit a distinct hematological profile, including anemia, eosinophilia, thrombocytopenia, and coagulopathy. Platelets, essential components of the hemostatic system, play a crucial role in the pathogenesis of schistosomiasis. Schistosomes secrete serine proteases and express ectoenzymes, such as calpain protease, alkaline phosphatase (SmAP), phosphodiesterase (SmNPP5), ATP diphosphohydrolase (SmATPDase1), serine protease Sk1, SmSP2, and Sm22.6, which can interfere with platelet normal functioning. This report provides comprehensive, up-to-date information on platelet abnormalities observed in patients with schistosomiasis, highlighting their importance in the disease progression and complications. It delves into the interactions between platelets and schistosomes, including the impact of platelet dysfunction on hemostasis and immune responses, immune-mediated platelet destruction, and the potential mechanisms by which schistosome tegumental ectoenzymes affect platelets. Furthermore, the report clarifies the relationship between platelet abnormalities and clinical manifestations such as thrombocytopenia, coagulation disorders, and the emergence of portal hypertension and gastrointestinal bleeding. Understanding the complex interplay between platelets and schistosomes is crucial for improving patient management and outcomes in schistosomiasis, particularly for those with platelet alterations. This knowledge contributes to improved diagnostic methods, innovative treatment strategies, and global efforts to control and eliminate schistosomiasis.

Bleeding risk assessment in immune thrombocytopenia.

The bleeding risk in immune thrombocytopenia (ITP) is related not only to low platelet count but also to the presence of platelet dysfunction. However, diagnosing a concomitant platelet dysfunction is challenging as most of the available platelet function assays (PFAs) require a platelet count of greater than 100,000/µL. Sonoclot coagulation and platelet function analyzer works on the principle of viscoelastometry, and results remain unaffected by the platelet counts. To assess the platelet function in adult acute ITP patients with the help of sonoclot coagulation and platelet function analyzer and correlate it with the risk of bleeding. Newly diagnosed acute ITP patients with a platelet count less than 20,000/µL were divided into two groups based on WHO bleeding grade: ITP non-bleeder (ITP-NB) group (WHO bleeding grade ≤1) and ITP bleeder (ITP-B) group (WHO bleeding grade ≥2). Platelet function was assessed by sonoclot in both groups. The patients without significant bleeding (ITP-NB) were followed up monthly for six months with the assessment of platelet function during each contact. Eighty patients (30 ITP-B and 50 ITP-NB) were prospectively included in this study. The median age of patients in the two groups was 37 years and 30 years, respectively. The female-to-male ratio was 4:1 and 1:1 in ITP-B and ITP-NB groups. The median platelet count in ITP-B and ITP-NB was 12000/µL (range 1000-19000/µL) and 8000/µL (range 1000-19000/µL), respectively. Mean platelet functions by sonoclot in both groups were lower than the normal cut-off (>1.6). However, the mean platelet function in the ITP-B group (0.2 + 0.17) was significantly lower than the ITP-NB group (1.2 ± 0.52) (p = 0.01). During the follow-up period of 6 months, patients in ITP-NB with a normal platelet function (>1.6) on sonoclot had lesser episodes (one episode) of clinically significant bleeding than patients with a low platelet function (4 episodes). Patients with acute severe thrombocytopenia and bleeding phenotype have a greater abnormality on platelet function by sonoclot than patients with non-bleeding phenotype. This information may help in taking therapeutic decisions in patients with acute ITP.

What can ex vivo experiments contribute to clinical haemostasis management?

A recent ex vivo study found that post-cardiopulmonary bypass platelet defects can be restored with supplemental fibrinogen, but the clinical significance of this finding will require further study. We propose that the best management strategy for achieving haemostasis in bleeding surgical patients is to identify individualised coagulation defects and then use a targeted therapeutic approach that addresses each identified defect systematically.

Supplemental fibrinogen restores thrombus formation in cardiopulmonary bypass-induced platelet dysfunction ex vivo.

BACKGROUND: Major cardiac surgery related blood loss is associated with increased postoperative morbidity and mortality. Platelet dysfunction is believed to contribute to post-cardiopulmonary bypass (CPB)-induced microvascular bleeding. We hypothesised that moderately hypothermic CPB induces platelet dysfunction and that supplemental fibrinogen can restore in vitro thrombus formation. METHODS: Blood from 18 patients, undergoing first-time elective isolated aortic valve surgery was drawn before CPB, 30 min after initiation of CPB, and after CPB and protamine administration, respectively. Platelet aggregation was quantified by optical aggregometry, platelet activation by flow-cytometric detection of platelet surface expression of P-selectin, annexin V, and activated glycoprotein IIb/IIIa, thrombus formation under flow and effect of supplemental fibrinogen (4 mg ml-1) on in vitro thrombogenesis. RESULTS: Post-CPB adenosine-diphosphate and TRAP-6-induced aggregation decreased by 40% and 10% of pre-CPB levels, respectively (P<0.0001). Although CPB did not change glycoprotein IIb/IIIa receptor expression, it increased the percentage of unstimulated P-selectin (1.2% vs 7%, P<0.01) positive cells and annexin V mean fluorescence intensity (15.5 vs 17.2, P<0.05), but decreased percentage of stimulated P-selectin (52% vs 26%, P<0.01) positive cells and annexin V mean fluorescence intensity (508 vs 325, P<0.05). Thrombus area decreased from 6820 before CPB to 5230 after CPB (P<0.05, arbitrary units [a.u.]). Supplemental fibrinogen increased thrombus formation to 20 324 and 11 367 a.u. before CPB and after CPB, respectively (P<0.001), thereby restoring post-CPB thrombus area to levels comparable with or higher than pre-CPB baseline. CONCLUSIONS: Single valve surgery using moderately hypothermic CPB induces partial platelet dysfunction. Thrombus formation was restored in an experimental study design by ex vivo supplementation of fibrinogen.

Unique case of successful surgical treatment of recurrent spinal epidural hematoma after lumbar disc surgery in a Glanzmann thrombasthenia patient.

We report a case of recurrent postoperative spinal hemorrhage after lumbar disc surgery in a Glanzmann thrombasthenia patient.

Acquired hemophilia A and delta storage pool deficiency in a patient with indolent non-Hodgkin lymphoma.

B-cell lymphoproliferative diseases may be associated with acquired hemostasis disorders, such as acquired hemophilia A (AHA) caused by autoantibodies that neutralize factor VIII activity, and δ-storage pool deficiency, an abnormality of platelet function due to defective dense granules and impaired secretion. We describe the case of a 67-year-old man in whom these two acquired bleeding disorders were concomitantly present as the first clinical manifestation of an indolent non-Hodgkin lymphoma. Immunosuppressive therapy with prednisone was initially started to eradicate anti-FVIII antibodies, subsequently boosted with cyclophosphamide and rituximab, these medications being also chosen to treat the associated indolent lymphoma. Bleeding symptoms were first tackled with limited benefit by using rFVIIa and then rescued using recombinant porcine FVIII. After a 6 month's follow-up lymphoma and AHA were in remission and platelet function was improved. This case underlines the need of multiple and complex diagnostic and therapeutic approaches to rare acquired bleeding disorders associated with lymphoproliferative diseases.

Left ventricular assist device implantation causes platelet dysfunction and proinflammatory platelet-neutrophil interaction.

Blood flow through left ventricular assist devices (LVAD) may induce activation and dysfunction of platelets. Dysfunctional platelets cause coagulation disturbances and form platelet-neutrophil conjugates (PNC), which contribute to inflammatory tissue damage. This prospective observational cohort study investigated patients, who underwent implantation of a LVAD (either HeartMate II (HM II) (n = 7) or HeartMate 3 (HM 3) (n = 6)) and as control patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) (n = 10). We performed platelet and leukocyte flow cytometry, analysis of platelet activation markers, and platelet aggregometry. Platelet CD42b expression was reduced at baseline and perioperatively in HM II/3 compared to CABG/AVR patients. After surgery the platelet activation marker ß-thromboglobulin and platelet microparticles increased in all groups while platelet aggregation decreased. Platelet aggregation was more significantly impaired in LVAD compared to CABG/AVR patients. PNC were higher in HM II compared to HM 3 patients. We conclude that LVAD implantation is associated with platelet dysfunction and proinflammatory platelet-leukocyte binding. These changes are less pronounced in patients treated with the newer generation LVAD HM 3. Future research should identify device-specific LVAD features, which are associated with the least amount of platelet activation to further improve LVAD therapy.

Efficacy of intra-articular injection of allogeneic platelet-rich plasma for knee osteoarthritis combined with hematologic blood dyscrasias with platelet dysfunction: protocol of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Autologous platelet-rich plasma (PRP) has been shown to alleviate the symptoms of patients suffering from knee osteoarthritis (KOA), but for certain patients with hematologic diseases with platelet dysfunction and patients receiving anti-platelet medications, autologous PRP is not an optimum solution. Allogeneic PRP has been proven to be safe and effective in the treatment of osteoarthritis, rotator cuff disease, refractory wounds and other medical fields. However, a well-designed and long-term follow-up prospective randomized controlled trial (RCT) to evaluate the effect of allogeneic PRP intra-articular injections for KOA combined with hematologic blood dyscrasias has not yet been performed. METHODS/ DESIGN: We will conduct an allogeneic PRP injection for KOA combined with hematologic blood dyscrasias with platelet dysfunction study: a prospective, randomized, double-blind, placebo-controlled trial. One hundred participants with KOA combined with hematologic blood dyscrasias with platelet dysfunction will be randomly allocated to receive either one allogeneic PRP injection or one saline injection into the knee joint. The primary outcome will be a 12-month change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. Secondary outcomes will be the 36-Item Short-Form General Health Survey (SF-36) score, Lysholm score, overall knee pain score and MRI assessment at 1-, 3-, 6- and 12-month. DISCUSSION: The results of this study will help determine whether allogeneic PRP could be used as a non-surgical intervention to treat patients with knee OA combined with hematologic blood dyscrasias with platelet dysfunction. TRIAL REGISTRATION: Chinese Clinical Trials Registry reference: ChiCTR2100048624. Prospectively registered 11th of July 2021.

Effectiveness of the scheduled transfusion strategy for factor V deficiency with platelet dysfunction during coronary artery surgery.

BACKGROUND: Factor V deficiency is a rare disease, with an incidence of one in a million. Symptoms are mostly scant, and it is often diagnosed by the presence of an abnormality on PT-INR or APTT. In addition, no established therapy exists and platelet dysfunction is seldom found to be concomitant with this disease CASE PRESENTATION: A 64-year-old man who had both factor V deficiency and platelet dysfunction had angina in the past year. Coronary surgery was required, and we successfully performed coronary artery bypass grafting under strategic planned platelet transfusion with additional adequate cryoprecipitates transfusion. No perioperative problems nor any postoperative major bleeding issues were observed. The postoperative course was also uneventful. CONCLUSION: Strategic planned platelet transfusion with the additional transfusion of an adequate amount of cryoprecipitates is thus considered to be feasible for cases presenting with factor V deficiency and platelet dysfunction.

Decreased Platelet Specific Receptor Expression of P-Selectin and GPIIb/IIIa Predict Future Non-Surgical Bleeding in Patients after Left Ventricular Assist Device Implantation.

Non-surgical bleeding (NSB) is one of the major clinical complications in patients under continuous-flow left ventricular assist device (LVAD) support. The increased shear stress leads to an altered platelet receptor composition. Whether these changes increase the risk for NSB is unclear. Thus, we compared the platelet receptor composition of patients with (bleeder group, n = 18) and without NSB (non-bleeder group, n = 18) prior to LVAD implantation. Blood samples were obtained prior to LVAD implantation and after bleeding complications in the post-implant period. Platelet receptor expression of GPIbα, GPIIb/IIIa, P-selectin and CD63 as well as intra-platelet oxidative stress levels were quantified by flow cytometry. Bleeders and non-bleeders were comparable regarding clinical characteristics, von Willebrand factor diagnostics and the aggregation capacity before and after LVAD implantation (p > 0.05). LVAD patients in the bleeder group suffered from gastrointestinal bleeding (33%; n = 6), epistaxis (22%; n = 4), hematuria or hematoma (17%; n = 3, respectively) and cerebral bleeding (11%; n = 2). Prior to LVAD implantation, a restricted surface expression of the platelet receptors P-selectin and GPIIb/IIIa was observed in the bleeder group (P-selectin: 7.2 ± 2.6%; GPIIb/IIIa: 26,900 ± 13,608 U) compared to non-bleeders (P-selectin: 12.4 ± 8.1%, p = 0.02; GPIIb/IIIa: 36,259 ± 9914 U; p = 0.02). We hypothesized that the reduced platelet receptor expression of P-selectin and GPIIb/IIIa prior to LVAD implantation may be linked to LVAD-related NSB.

Screening for Platelet Dysfunction and Use of Prophylactic Tranexamic Acid in Patients Undergoing Deep Brain Stimulation: A Retrospective Analysis of Incidence and Outcome of Intracranial Hemorrhage.

INTRODUCTION: The rate of intracranial hemorrhage (ICH) after deep brain stimulation (DBS) is between 1.5 and 6.1%, with prolonged deficits occurring in 0.4-2.5% of the patients. This retrospective study investigates whether the prophylactic administration of tranexamic acid (TA) to patients with abnormal platelet function detected preoperatively by platelet function analyzer (PFA) lowered the risk for an ICH event. METHODS: We performed a systematic review of the medical records of 485 consecutively admitted patients who underwent bilateral DBS surgery in a single-center university hospital setting between 2009 and 2018. The cohort was split into two groups. In one group, preoperative PFA screening was performed (n = 156, patients recruited from 2014 to 2018), and TA was administered if platelet function was abnormal. No preoperative PFA was performed in the second group (n = 359, patients recruited from 2009 to 2013). Both cohorts were analyzed for the occurrence of ICH, defined by (i) detection of ICH in routine postoperative magnetic resonance/computed tomography imaging or (ii) in non-routine imaging for the onset of new neurological symptoms. RESULTS: Fourteen of the 156 screened patients (9%) showed reproducible PFA-100 closure abnormalities (3 with von Willebrand disease, 11 with no identifiable cause of platelet dysfunction). Two of the 156 patients (1.3%) in this cohort revealed an ICH on imaging, 1 of whom (0.6%) exhibited a prolonged neurological deficit as a result of ICH. In the cohort without platelet testing, 11 of the 329 patients (3.3%) demonstrated ICH on imaging, of whom 5 (1.5%) suffered from a prolonged neurological deficit. CONCLUSION: In this retrospective study, the screening and the administration of TA appeared to lower the risk of an ICH by 1.8%. One patient with von Willebrand disease suffered an ICH despite TA treatment. A prospective study is needed to clarify the impact of platelet testing and TA administration on the of incidence ICH.

Susceptibility-directed anticoagulation after pancreas transplantation: A single-center retrospective study.

Pancreas transplant achieves consistent long-term euglycemia in type 1 diabetes. Allograft thrombosis (AT) causes the majority of early graft failure. We compared outcomes of four anticoagulation regimens administered to 95 simultaneous kidney-pancreas or isolated pancreas transplanted between 1/1/2015 and 11/20/2018. Early postoperative anticoagulation regimens included the following: none, subcutaneous heparin/aspirin, with or without dextran, and heparin infusion. The regimens were empirically selected based on each surgeon's assessment of hemostasis of the operative field and personal preference. A sonographic-based global scoring system of AT is presented. The 47-month recipients and graft survival were 95% and 86%, respectively. Recipients with or without AT had similar survival. Five and four grafts were lost due to death and AT, respectively. Outcomes of prophylaxis regimens correlated with intensity of anticoagulation. Compared with no anticoagulation, an increase in hemorrhagic complications occurred exclusively with iv heparin. The higher arterial AT score found in regimens lacking antiplatelet therapy highlights the importance of early antiaggregants therapy. Abnormal fibrinolysis was associated with an increase in AT score. Platelet dysfunction, warm ischemia time, and enteric drainage were predictive of AT and, along with other known risk factors, were incorporated into an algorithm that matches intensity of early postoperative anticoagulation to the thrombotic risk.

Novel insights into the assessment of risk of upper gastrointestinal bleeding in decompensated cirrhotic children.

OBJECTIVES: Cirrhotic children wait-listed for liver transplant are prone to bleeding from gastrointestinal varices. Grade 2-3 esophageal varices, red signs, and gastric varices are well-known risk factors. However, the involvement of hemostatic factors remains controversial because of the rebalanced state of coagulation during cirrhosis. METHODS: Children suffering from decompensated cirrhosis were prospectively included while being on waitlist. Portal hypertension was assessed by ultrasound and endoscopy. Coagulopathy was evaluated through conventional tests, thromboelastometry, and platelet function testing. The included children were followed up until liver transplantation, and all bleeding episodes were recorded. Children with or without bleeding were compared according to clinical, radiological, endoscopic, and biological parameters. In addition, validation of a predictive model for risk of variceal bleeding comprising of grade 2-3 esophageal varices, red spots, and fibrinogen level <150 mg/dL was applied on this cohort. RESULTS: Of 20 enrolled children, 6 had upper gastrointestinal bleeding. Significant differences were observed in fibrinogen level, adenosine diphosphate, and thrombin-dependent platelet aggregation. The model used to compute the upper gastrointestinal bleeding risk had an estimated predictive performance of 81.0%. Platelet aggregation analysis addition improved the estimated predictive performance up to 89.0%. CONCLUSIONS: We demonstrated an association between hemostatic factors and the upper gastrointestinal bleeding risk. A low fibrinogen level and platelet aggregation dysfunction may predict the risk of bleeding in children with decompensated cirrhosis. A predictive model is available to assess the upper gastrointestinal bleeding risk but needs further investigations. Clinicaltrials.gov number: NCT03244332.

De novo variant in tyrosine kinase SRC causes thrombocytopenia: case report of a second family.

A germline heterozygous gain-of-function p.E527K variant in tyrosine kinase SRC was previously found to cause thrombocytopenia, myelofibrosis, bleeding, bone pathologies, premature edentulism and mild facial dysmorphia in nine patients of a single pedigree. Because of this variant, SRC loses its self-inhibitory capacity, causing constitutively active SRC expression in platelets. These patients have fewer and heterogeneous-sized platelets that are hyporeactive to collagen. We now report a 5-year-old girl with syndromic thrombocytopenia due to the same SRC-E527K variant that occurs de novo. A bone marrow biopsy, blood smear analysis, platelet aggregations, flow cytometric analysis of P-selectin, SRC expression and tyrosine phosphorylation studies were performed to confirm the similarities between the two families. This study strengthens our previous finding that hyperactive SRC kinase results in mild platelet dysfunction and thrombocytopenia with hypogranular platelets and further expands the clinical description of this syndrome to improve early recognition.

RASGRP2 gene variations associated with platelet dysfunction and bleeding.

This manuscript reviews pathogenic variants in RASGRP2, which are the cause of a relatively new autosomal recessive and nonsyndromic inherited platelet function disorder, referred to as platelet-type bleeding disorder-18 (BDPLT18)(OMIM:615888). To date, 18 unrelated BDPLT18 pedigrees have been reported, harboring 19 different homozygous or compound heterozygous RASGRP2 variants. Patients with this disease present with lifelong moderate to severe bleeding, with epistaxis as the most common and relevant bleeding symptom. Biologically, they exhibit normal platelet count and morphology, reduced aggregation responses to ADP, epinephrine and low-dose collagen, and impaired αIIbß3 integrin activation (fibrinogen or PAC-1 binding) in response to most agonists except PMA. Diagnosis is confirmed by genetic analysis of RASGRP2.

High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity.

Thrombosis and bleeding are devastating adverse events in patients supported with blood-contacting medical devices (BCMDs). In this study, we delineated that high non-physiological shear stress (NPSS) caused platelet dysfunction that may contribute to both thrombosis and bleeding. Human blood was subjected to NPSS with short exposure time. Levels of platelet surface GPIbα and GPVI receptors as well as activation level of GPIIb/IIIa in NPSS-sheared blood were examined with flow cytometry. Adhesion of sheared platelets on fibrinogen, von Willibrand factor (VWF), and collagen was quantified with fluorescent microscopy. Ristocetin- and collagen-induced platelet aggregation was characterized by aggregometry. NPSS activated platelets in a shear and exposure time-dependent manner. The number of activated platelets increased with increasing levels of NPSS and exposure time, which corresponded well with increased adhesion of sheared platelets on fibrinogen. Concurrently, NPSS caused shedding of GPIbα and GPVI in a manner dependent on shear and exposure time. The loss of intact GPIbα and GPVI increased with increasing levels of NPSS and exposure time. The number of platelets adhered on VWF and collagen decreased with increasing levels of NPSS and exposure time, respectively. The decrease in the number of platelets adhered on VWF and collagen corresponded well with the loss in GPIbα and GPVI on platelet surface. Both ristocetin- and collagen-induced platelet aggregation in sheared blood decreased with increasing levels of NPSS and exposure time. The study clearly demonstrated that high NPSS causes simultaneous platelet activation and receptor shedding, resulting in a paradoxical effect on platelet function via two distinct mechanisms. The results from the study suggested that the NPSS could induce the concurrent propensity for both thrombosis and bleeding in patients.

The association between platelet dysfunction and adverse outcomes in cardiac surgical patients.

Haemostatic activation during cardiopulmonary bypass is associated with prothrombotic complications. Although it is not possible to detect and quantify haemostatic activation directly, platelet dysfunction, as measured with point-of-care-assays, may be a useful surrogate. In this study, we assessed the association between cardiopulmonary bypass-associated platelet dysfunction and adverse outcomes in 3010 cardiac surgical patients. Platelet dysfunction, as measured near the end of the rewarming phase of cardiopulmonary bypass, was calculated as the proportion of non-functional platelets after activation with collagen. Logistic regression and multivariable analyses were applied to assess the relationship between platelet dysfunction and a composite of in-hospital death; myocardial infarction; stroke; deep vein thrombosis or pulmonary embolism; and acute kidney injury (greater than a two-fold increase in creatinine). The outcome occurred in 251 (8%) of 3010 patients. The median (IQR [range]) percentage platelet dysfunction was less for those without the outcome as compared with those with the outcome; 14% (8-28% [1-99%]) vs. 19% (11-45% [2-98%]), p < 0.001. After risk adjustment, platelet dysfunction was independently associated with the composite outcome (p < 0.001), such that for each 1% increase in platelet dysfunction there was an approximately 1% increase in the composite outcome (OR 1.012; 95%CI 1.006-1.018). This exploratory study suggests that cardiopulmonary bypass-associated platelet dysfunction has prognostic value and may be a useful clinical measure of haemostatic activation in cardiac surgery.

The effect of a novel turbulence-controlled suction system in the prevention of hemolysis and platelet dysfunction in autologous surgery blood.

BACKGROUND: Re-transfusion of autologous blood is an important aspect of intraoperative blood management. Hemolysis and platelet dysfunction due to turbulence in the blood suction system strongly impede later usage of suction blood for re-transfusion. The aim of this study was to analyze the effects of a novel surgical-blood suction system with an automatic control setup for minimization of turbulence in the blood flow. METHODS: We compared the turbulence-controlled suction system (TCSS) with a conventional suction system and untreated control blood in vitro. Blood cell counts, hemolysis levels according to free hemoglobin (fHb) and platelet function were analyzed to determine the integrity of the suction blood. RESULTS: In the conventional suction system, we found a strong increase of the fHb levels. In contrast, erythrocyte integrity was almost completely preserved when using the TCSS. We obtained similar results regarding platelet function. The expression of platelet glycoproteins, such as GP IIb/IIIa and P-selectin, native or after stimulation with ADP, were markedly impaired by the conventional system, but not by the TCSS. In addition, platelet aggregometry revealed significant platelet dysfunction in conventional suction blood, but less aggregation impairments were present in blood samples from the TCSS. CONCLUSION: Our findings on an in vitro assessment show major improvements in red blood cell integrity and platelet function of suction blood when using the TCSS compared to a conventional suction system. These results reflect a significant benefit for autologous re-transfusion. We suggest testing the TCSS in surgery for clinical evaluation.