Platelet dysfunction on thromboelastogram is associated with severity of blunt traumatic brain injury.

BACKGROUND: Platelet dysfunction associated with isolated traumatic brain injury (TBI) can be measured using thromboelastography-platelet mapping (TEG-PM). We hypothesized that platelet dysfunction can be detected after blunt TBI, and the degree of dysfunction is associated with increased TBI severity and in-hospital mortality. METHODS: This was a retrospective review of adult trauma patients admitted to a single level 1 trauma center from August 2013 to March 2015 who suffered isolated severe blunt TBI. Subjects were included if they received a TEG-PM within 24 h from injury, and excluded if on preinjury antiplatelet medications. RESULTS: 119 subjects were analyzed. Severe TBI subjects (AIS-head 5) had ADPi 18.4 points higher than moderate TBI subjects (AIS-head 3) (p = 0.001). Platelet dysfunction was not associated with TBI progression. ADPi significantly predicted mortality (OR 1.033; 95% CI 1.005-1.061, p = 0.02). CONCLUSION: Platelet dysfunction occurs immediately after isolated blunt TBI, is more pronounced with increasing TBI severity, and is associated with higher odds of in-hospital mortality. Further investigation is needed to determine whether this is a marker of disease severity or a therapeutic target.

Poorer prognosis with ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia: a single-center case-control study.

In ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia (PTCP), automated platelet counts are lower than actual counts because of EDTA-induced aggregation. Factors contributing to the incidence of EDTA-PTCP are unknown, and no study has assessed the prognosis of EDTA-PTCP patients. This retrospective study assessed characteristics in EDTA-PTCP patients and matched controls to determine differences in prognosis. A retrospective case-control study was designed. From the University of Tokyo Hospital database, we identified patients diagnosed with EDTA-PTCP between 2009 and 2012, and performed 1:2 case:control matching for age and sex. A control group of sex- and age-matched patients was selected at random from the same database. We investigated differences in the frequency of complications, medication history, and blood transfusion history between the groups at the time of blood collection. Prognosis was evaluated using multivariate Cox regression analysis adjusting for age, sex, autoimmune disease, liver disease, and malignant tumor. We identified 104 EDTA-PTCP patients and 208 matched controls. The median age was 69.0 years (interquartile range: 54-76), with men comprising 51%. EDTA-PTCP patients had a higher frequency of malignant tumor and a lower frequency of hypertension and diabetes than controls. After adjustment for background factors, prognosis of EDTA-PTCP patients was significantly poorer than controls (hazard ratio, 11.8; 95% confidence intervals, 2.62-53.54). In conclusion, EDTA-PTCP patients had higher mortality, and EDTA-PTCP may need to be recognized as an indicator of worse prognosis.

High flow velocity through congenital cardiac lesions predicts preoperative platelet dysfunction.

BACKGROUND: Platelet dysfunction resulting from abnormal fluid shear stress has been reported in adults with aortic stenosis. Blood flowing through a congenital heart defect at greater than normal velocity is subjected to increased shear stress. The primary aim was to determine whether peak flow velocity through congenital cardiac lesions predicts preoperative platelet dysfunction. METHODS: The charts of 402 patients who underwent cardiopulmonary bypass and had preoperative platelet function analysis were evaluated. Platelet dysfunction was measured as a prolonged closure time (CT) in seconds with a platelet function analyzer. Echocardiography was used to determine peak velocity. The relationship between peak velocity and CT was analyzed using linear regression and Kaplan-Meier estimation. RESULTS: The distribution of peak velocity was bimodal. The mean velocity of the lower group was 1.9 m/second and the higher group was 4.2 m/second. Univariate analysis showed age, weight, peak velocity, hematocrit, and Risk Adjustment for Congenital Heart Surgery score to be associated with prolonged CT. Using multivariable analysis, prolonged CT was significantly associated with peak velocity (p < 0.001). For each 1m/second increase in peak velocity the CT increased by over 9 seconds (p < 0.001). In addition, a median CT increase of more than 6 seconds was also associated with a 5 percentage point drop in hematocrit (p = 0.04). CONCLUSIONS: Platelet dysfunction is associated with high blood flow velocity through congenital cardiac lesions. Lower preoperative hematocrit was associated with prolonged CT, which may suggest subclinical bleeding secondary to platelet dysfunction.

Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality.

While platelets are primary mediators of hemostasis, there is emerging evidence to show that they may also mediate pathologic thrombogenesis. Little data are available on risks and benefits associated with platelet transfusions in thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT) and immune thrombocytopenic purpura (ITP). This study utilized the Nationwide Inpatient Sample to evaluate the current in-hospital platelet transfusion practices and their association with arterial/venous thrombosis, acute myocardial infarction (AMI), stroke, and in-hospital mortality over 5 years (2007-2011). Age and gender-adjusted odds ratios (adjOR) associated with platelet transfusions were calculated. There were 10 624 hospitalizations with TTP; 6332 with HIT and 79 980 with ITP. Platelet transfusions were reported in 10.1% TTP, 7.1% HIT, and 25.8% ITP admissions. Platelet transfusions in TTP were associated with higher odds of arterial thrombosis (adjOR = 5.8, 95%CI = 1.3-26.6), AMI (adjOR = 2.0, 95%CI = 1.2-3.3) and mortality (adjOR = 2.0,95%CI = 1.3-3.0), but not venous thrombosis. Platelet transfusions in HIT were associated with higher odds of arterial thrombosis (adjOR = 3.4, 95%CI = 1.2-9.5) and mortality (adjOR = 5.2, 95%CI = 2.6-10.5) but not venous thrombosis. Except for AMI, all relationships remained significant after adjusting for clinical severity and acuity. No associations were significant for ITP. Platelet transfusions are associated with higher odds of arterial thrombosis and mortality among TTP and HIT patients.

Patients with severe aortic valve stenosis and impaired platelet function benefit from preoperative desmopressin infusion.

BACKGROUND: Patients with severe aortic valve stenosis have a markedly reduced platelet function as measured by a prolonged collagen adenosine diphosphate closure time (CADP-CT) determined by the platelet function analyzer PFA-100. We hypothesized that such patients may benefit from desmopressin when they present with prolonged CADP-CT due to the specific action of desmopressin on von Willebrand factor (VWF) and CADP-CT. METHODS: In this double-blind, randomized placebo controlled trial, 43 patients undergoing aortic valve replacement (due to severe aortic valve stenosis with CADP-CT>170 seconds) were given desmopressin 0.3 µg/kg or saline intravenously after induction of anesthesia. Measurement of CADP-CT, factor VIII activity, von Willebrand factor antigen, GpIb binding activity, ristocetin cofactor activity, collagen-binding activity, and multimers were performed after induction of anesthesia, one hour after desmopressin infusion, and 24 hours postoperatively. RESULTS: In the majority of patients, baseline values of von Willebrand factor related indices were normal, but increased one hour after infusion of desmopressin by 73% to 90% as compared with placebo. Selective loss of high molecular weight multimers was seen only in a minority of patients. The CADP-CT was greater than 170 seconds in 92% of screened patients, and desmopressin shortened CADP-CT by 48% versus baseline and reduced postoperative blood loss by 42% (p<0.001). CONCLUSIONS: Prolonged CADP-CT indicates platelet dysfunction in severe aortic valve stenosis, and can guide the use of desmopressin as an effective prohemostatic agent in patients with severe aortic valve stenosis.

Thrombotic microangiopathy as a complication of high-dose chemotherapy for breast cancer.

Five hundred and eighty-one patients with stage II-IV breast cancer were treated at Duke University Medical Center with high-dose chemotherapy, followed by hematopoietic support. All patients received a conditioning regimen of cyclophosphamide, cisplatin and carmustine. Of these patients, 15 (2.6%) developed symptoms similar to the hemolytic-uremic syndrome with evidence of thrombotic microangiopathy (TMA). The time of onset ranged from 75 days to 281 days post-transplant, with a median of 143 days. Hemolytic anemia and thrombocytopenia, without alternative cause, were required for diagnosis. All patients were treated with steroid therapy. In addition, 12 patients were treated primarily with plasmapheresis, and received a median of 46 treatments. Additional therapy included staphylococcal protein A column apheresis (eight patients), vincristine (three patients) and danazol (one patient). The mortality rate was 11 of 15 patients (73%). These patients had a median survival of 41 days from diagnosis of TMA (range 2-76 days). The four survivors are alive at 76, 186, 1837 and 2387 days from diagnosis of TMA. Three of these patients received twice daily plasmapheresis and protein A column apheresis therapy. One patient recovered without specific therapy. TMA is an infrequent complication of high-dose chemotherapy, but is associated with a high mortality. It frequently follows significant pulmonary drug toxicity. Survival may be improved with early diagnosis and aggressive plasmapheresis therapy.

The syndrome of pneumococcemia, disseminated intravascular coagulation and asplenia.

A 58-year-old man who survived an episode of fulminant pneumococcal septicemia with disseminated intravascular coagulation had undergone splenectomy 23 years previously. In the literature there are 25 reported cases of fulminant septicemia and disseminated intravascular coagulation associated with asplenia in adults (excluding cases in which corticosteroid or immunosuppressive therapy was given). The pneumococcus was responsible for all of these cases as well. The mortality in this series was more than 90%, and death occurred within 24 hours of presentation at hospital in almost 70% of the fatal cases and was associated with high-density bacteremia and adrenal hemorrhage. Gram-staining of the buffy coat of the peripheral blood or the exudate from purpuric skin lesions was carried out in only 6 of the 26 cases but yielded positive results in all but 1. It is concluded that a diagnosis of septicemia in asplenic adults can be established within a short time of presentation on the basis of statistical probability and the results of Gram-staining of the peripheral blood and exudate from the skin lesions. Prevention appears to be the cornerstone of management because of the variable interval from splenectomy to the onset of the syndrome and the high mortality.