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Objectives Many patients admitted with an ischemic stroke or transient ischemic attack (TIA) undergo thrombophilia testing. There is limited evidence to support this practice. We examined the effect of thrombophilia testing on management of patients admitted with an ischemic stroke or TIA. Materials and Methods In this retrospective observational single-center study, we identified patients who were admitted with stroke or TIA and underwent thrombophilia testing over a 45-month period. We reviewed their electronic medical records to assess whether testing affected clinical management, defined as anticoagulation treatment by the time of discharge due to a positive test result. Secondary endpoints included potential misdiagnosis due to false positive results and cost of testing. Results Testing was performed in 143 patients with a stroke or TIA. Forty-four patients (31%) had at least 1 positive test result. The most common positive tests were an elevated factor VIII activity (18% of patients tested) and decreased protein S activity (11% of patients tested). Both of these tests are subject to acute phase effects. Testing altered clinical management in only 1 patient (1% of total patients tested). Thirty-three patients (75%) have the potential for carrying a misdiagnosis due to a positive test that was never repeated for confirmation or repeated too soon after the initial positive test. The annual cost of testing was approximately $62,000. Conclusions Thrombophilia testing in the acute inpatient setting rarely impacted the clinical management of patients admitted with a stroke or TIA. By avoiding thrombophilia testing, both the potential for misdiagnosis and health care costs can be reduced. Therefore, we have discontinued thrombophilia testing in in-patients with a diagnosis of stroke.

Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry. He was treated with aspirin (325 mg daily) and clopidogrel (75 mg daily) with no additional bleeding or thrombotic complications throughout his admission. This case provides further evidence that moderate to severe FVII deficiency does not protect against thrombosis.

BACKGROUND It is unknown how pooled platelets (PPs) compare to random apheresis platelets (RAPs) when HLA-selected platelets (PLTs) are unavailable for HLA-sensitized patients. The aim of this study was to compare patient responses to RAPs, HLA-selected PLTs, and PPs in HLA-sensitized patients. STUDY DESIGN AND METHODS This is a single-institution retrospective study of patients from January 2014 to April 2017 with a class I calculated panel-reactive antibody of 60% or more. Response to transfusion was determined by a corrected count increment (CCI) up to 1 hour after completion of transfusion. A CCI of 5 or more was considered successful. RESULTS Seventy-seven units of RAPs, 412 units of HLA-selected PLT, and 388 units PPs were transfused. Mean CCIs when transfusing RAPs, HLA-selected PLTs, and PPs were 2.82, 11.44, and 4.77, respectively (p

BACKGROUND Factor V (FV) deficiency may be inherited as an autosomal recessive disease or acquired as a result of autoantibody formation, either spontaneously or secondary to exposure to bovine thrombin or medications. Congenital FV deficiency has traditionally been treated with plasma transfusions. However, recent evidence has suggested that platelet (PLT) transfusions may be a better alternative as FV stored within PLT alpha granules has greater procoagulant potential and is released locally at sites of vascular injury. We report three cases of FV deficiency, one congenital and two acquired, and emphasize the different management approaches. CASE REPORTS Patient 1 was a 30-year-old man with congenital FV deficiency who presented with a trauma-induced hematoma of his lower extremity. He was treated with 5 PLT units over 48 hours. Patient 2 was a 64-year-old woman who presented with an upper-extremity thrombus and was discovered to have a FV inhibitor, likely secondary to antibiotics. Patient 3 was a 75-year-old woman with hepatitis C virus (HCV) who presented with minor ecchymosis and was found to have a FV inhibitor secondary to either HCV or antibiotic exposure. Corticosteroids alone were able to eradicate the inhibitors in both patients with acquired inhibitors. CONCLUSIONS FV deficiency can present with a diverse range of symptoms. For bleeding patients, PLT transfusions should be the initial therapy. In patients with thrombosis, the risks and benefits of anticoagulation must be carefully assessed before treatment. For patients with minor bleeds, transfusions may be withheld, and elimination of the inhibitor should be the primary objective.

The liver plays a pivotal role in hemostasis. Consequently, patients with cirrhosis frequently demonstrate abnormal coagulation profiles on routine laboratory tests. These tests mainly reflect decreased procoagulant proteins. However, in cirrhosis, complex changes also occur in anticoagulant and fibrinolytic pathways. Recent evidence demonstrates that patients with cirrhosis exist in a state of hemostatic rebalance. Accordingly, routine tests inadequately represent hemostatic alterations in these patients. Unfortunately, these tests are regularly used to guide the transfusion of blood components with the assumption that they will correct laboratory abnormalities and improve hemostasis in a bleeding patient or prevent excessive bleeding following a procedure. With an absence of both accurate laboratory testing to assess hemostasis and evidence-based guidelines to direct the transfusion of blood components, management of patients with cirrhosis poses a significant challenge to clinicians. Therefore, we developed multidisciplinary guidelines for the periprocedural transfusion of blood components in patients with cirrhosis based on concurrent evidence and personal experience at our medical center.

Objectives Acute hypertriglyceridemia induced pancreatitis (HTP) presents with a more severe clinical course compared to other etiologies of pancreatitis. Therapeutic plasma exchange (TPE) is a potential treatment option for lowering plasma triglycerides and possibly decreasing morbidity and mortality. However, clinical data regarding its effectiveness are limited. Methods We retrospectively examined the clinical data and outcomes of 13 consecutive episodes of HTP in which TPE was employed to reduce plasma triglycerides during a 15-month period. Results The TPE was initiated at a median of 19 hours from the time of presentation. We performed 1.2–1.5 volume TPEs with 5% albumin as the replacement fluid. After only one TPE procedure, the mean plasma triglycerides values decreased from 2993 mg/dl to 487 mg/dl with a reduction of 84%. All 13 patients survived with a mean length of hospital stay of 9.5 days. There were no complications related to TPE. Conclusions One TPE procedure is an effective method for reducing plasma triglycerides and possibly decreases the length of hospital stay in patients admitted with HTP.

Warm autoantibodies (WAAs) are typically immunoglobulin G (IgG) antibodies directed against red blood cells (RBCs) that react maximally at 37 °C. They are detected in 1:1000 to 1:50,000 of pregnancies. WAAs may rarely cause a warm autoimmune hemolytic anemia (WAIHA), but most WAAs do not result in hemolysis. If WAAs are detected in a pregnant patient, the patient should be evaluated for RBC hemolysis. If there is hemolysis, the patient should be referred to a hematologist for further care. If there is no hemolysis, the patient may be managed similar to a pregnant patient that does not have red cell antibodies.

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.

The liver plays a pivotal role in hemostasis. Consequently, patients with cirrhosis frequently demonstrate abnormal coagulation profiles on routine laboratory tests. These tests mainly reflect decreased procoagulant proteins. However, in cirrhosis, complex changes also occur in anticoagulant and fibrinolytic pathways. Recent evidence demonstrates that patients with cirrhosis exist in a state of hemostatic rebalance. Accordingly, routine tests inadequately represent hemostatic alterations in these patients. Unfortunately, these tests are regularly used to guide the transfusion of blood components with the assumption that they will correct laboratory abnormalities and improve hemostasis in a bleeding patient or prevent excessive bleeding following a procedure. With an absence of both accurate laboratory testing to assess hemostasis and evidence-based guidelines to direct the transfusion of blood components, management of patients with cirrhosis poses a significant challenge to clinicians. Therefore, we developed multidisciplinary guidelines for the periprocedural transfusion of blood components in patients with cirrhosis based on concurrent evidence and personal experience at our medical center.

Introduction: Acquired hemophilia A (AHA) is a rare (1.5 per million/year) autoimmune disorder due to formation of spontaneous antibodies against factor VIII (FVIII) with an estimated mortality of 8-22%. First-line hemostatic agents to control a bleed include activated prothrombin complex concentrate (aPCC) and recombinant activated factor VII (rVIIa) whereas immunosuppressive therapy to eradicate the inhibitor include prednisone, cyclophosphamide, and rituximab. We present data on 12 AHA patients from our institution. Methods: We conducted a retrospective review of patients with AHA from January 1, 2010 to July 1, 2016. Results: Eight women and 4 men with a median age of 68 years (range 29-88 years) were included in the study. AHA was idiopathic in 7 patients, others being associated with HIV/Hepatitis C (1), Hepatitis C only (1), lymphoma (1) pregnancy (1), and pregnancy/systemic lupus erythematosus (SLE) (1). Of the 12 patients, 11 were admitted at least once with a bleeding episode. In total, there were 38 bleeding episodes, with 15 being characterized as severe (39%). The most common site of bleeding was deep muscle (50%), and 71% of bleeding episodes were considered spontaneous. The median FVIII activity at admission was Table 1 summarizes the number of bleeding episodes and immunosuppression for each patient. Patient 7 experienced 24 bleeding episodes with 23 requiring both aPCC (median 75 u/kg, range 50-80 u/kg) and rVIIa (median 50 mcg/kg, range 50-90 mcg/kg) alternating every 6 hours. This patient had breakthrough bleeds on either aPCC or rFVIIa but responded to the alternating regimen. Patient 11 developed severe bleeding in his upper extremities, necessitating bilateral upper extremity amputation. He was initially treated with only aPCC (100u/kg every 12 hours for 11 doses total); however, concern for disseminated intravascular coagulation prompted aPCC discontinuation. He received a total 121 doses of rVIIa (90mcg/kg every 2-4 hours) during his hospital stay. Patient 2 required two doses of rVIIa (90 mcg/kg every 12 hours) after having continued bleeding despite treatment with 11 doses of aPCC (50u/kg every 12 hours). Ten bleeding episodes were treated with only aPCC with a median 8 doses (range 2-16 doses), while 1 bleeding episode was controlled with only rVIIa. One bleeding episode did not require treatment. The median dosage of aPCC (with or without rVIIa) was 75u/kg (range 50-100 u/kg) given every 12 hours (range 8-24 hours) for 8 doses (range 1 -16 doses). The median dosage of rVIIa when used in conjunction with aPCC was 50mcg/kg (range 50-100 mcg/kg) given every 12 hours (range 4-24 hours) for 6 doses (range 1-13 doses). No patient experienced a thromboembolic event. Follow-up data was available for 9 patients (Table 1). Six patients achieved complete remission (CR) at a median 126 days (range 68-1103 days). Patient 12 was initially treated with 1mg/kg prednisone; however, upon tapering, her FVIII activity shortened from 114% to 36%. Cyclophosphamide (2mg/kg) was added with eventual inhibitor eradication. Patients 3 and 7 failed to attain CR and were treated with prednisone, cyclophosphamide, and rituximab. They continued to have a FVIII activity Conclusion: CR was achieved in 6 of 9 patients with follow-up data. There were no deaths related to AHA. A combination of aPCC and rVIIa, alternating every 6 hours, can safely be used to treat severe bleeding, reducing drug and administrative costs. Disclosures Sarode: CSL Behring: Consultancy, Honoraria.

Introduction: Platelet aggregation studies (PAS) are an important and underutilized diagnostic test (due to non-availability in most clinical laboratories and the requirement to be performed within 4 hours of sample collection) used in the evaluation of unexplained mucocutaneous type of bleeding after ruling out von Willebrand disease. Platelet aggregation studies are typically performed by one of two methods: impedance method using whole blood aggregometry (WBA) and light transmission aggregometry (LTA) using platelet rich plasma (PRP). WBA confers several advantages over LTA. First, it does not require centrifugation, which not only reduces testing time by half, but also avoids platelet activation and loss of giant thrombocytes. Second, in vivo conditions are better replicated reflecting the natural milieu including red and white blood cells, which are known to affect platelet function in vivo. In addition, WBA requires smaller blood volume making testing feasible for neonates and pediatric patients. Lastly, simultaneous assessment of platelet ATP release is performed to assess secretion defects. Despite these advantages, WBA is not commonly used. Aims: To analyze our data to further support the diagnostic utility of WBA in identifying platelet dysfunction as the etiology of bleeding tendencies. Methods: A retrospective chart review of patients on whom PAS were performed between June 2011 and September 2014. Results: We performed 202 PAS on 162 patients. 82% of patients were females and the average age was 28 years (range 9 months-87 years). 24 (15%) patients were pediatric (range 9 months-18 years). 83 of 162 (51%) patients had abnormal results (52% of adults and 50% of the pediatric cases). 26 of the 162 (16%) patients had repeat studies performed. Of these patients, 77% (20/26) had reproducible findings that confirmed the previous results. 8% (2/26) had normalized platelet function after discontinuation of medications (e.g. statins, fish oil, selective serotonin reuptake inhibitor) known to induce platelet dysfunction. 15% (4/26) had different responses to agonists on repeat testing. Abnormal WBA studies revealed decreased to absent responses to various agonists described in table 1. In patients on selective serotonin release inhibitors (SSRIs), there was a spectrum of responses to agonists; the most common abnormality was global dysfunction. Abnormalities to single agonists, such as ADP and AA, were also seen in patients taking SSRIs. Non-steroidal anti-inflammatory drugs affected aggregation with arachidonic acid (AA) and AA+ADP. Statins affected aggregation with AA alone, AA+ADP and AA+ATP secretion. 3 patients had platelet dysfunction consistent with Acquired Glanzmann's Syndrome due possibly to autoantibodies in the setting of chronic lymphocytic leukemia. Conclusion: Over 50% patients tested by WBA had abnormal platelet function giving high positive predictive value for this test in a selected group of patients who otherwise would have carried a non-specific bleeding diagnosis with non-specific treatment. Table 1. Distribution of Agonists Eliciting Impaired Responses Agonists Eliciting Impaired Response Number of Studies with Abnormal Results AA+Collagen (Aspirin like defect) 27 (23%) AA+Collagen+ADP 22 (18%) AA+ADP 21 (17%) AA+Collagen+ADP+Ristocetin (Global dysfunction) 19 (15%) ADP 11 (9%) AA 7 (6%) ADP+Collagen 4 (3%) AA+ADP+Ristocetin 3 (2%) Decreased ATP Secretion 8 (7%) AA=Arachidonic Acid Disclosures No relevant conflicts of interest to declare.