Karen Matevosyan

Rapid warfarin reversal: a 3-factor prothrombin complex concentrate and recombinant factor VIIa cocktail for intracerebral hemorrhage

OBJECT Intracerebral hemorrhage (ICH) is the most serious bleeding complication of vitamin K antagonist (VKA) therapy, carrying a high mortality. Rapid reversal of VKA in ICH is critical. Plasma therapy, the standard of care in the US, is not optimal. The ideal prothrombin complex concentrate (PCC) containing all vitamin K-dependent factors (VKDFs) is not available in the US. Therefore, the authors developed a Trauma Coumadin Protocol (TCP) consisting of a 3-factor PCC available in the US (which contains insufficient factor VII [FVII]) with a low-dose recombinant FVIIa to rapidly reverse VKA. METHODS Forty-six patients treated with the TCP were retrospectively analyzed. Fourteen patients had pre- and post-TCP plasma samples collected to assess their VKDF increment. Eleven patients had measurable intraparenchymal hematomas, which were evaluated for expansion. RESULTS The mean pre- and post-TCP international normalized ratios (INRs) were 3.4 (median 2.9) and 1.0 (median 0.9), respectively. Once corrected, INR was maintained at < 1.3 during a patients hospital stay. The pre-TCP median values of FII, FVII, FIX, and FX were 28%, 21%, 45%, and 20%, respectively; post-TCP median values increased to 144%, 417%, 102%, and 143%, respectively. Four of the 11 patients with measurable intraparenchymal hemorrhage had expansion at 24 hours after TCP. One patient probably (8 hours post-TCP) and 1 patient possibly (3 days post-TCP) had thrombotic complications. CONCLUSIONS The TCP was very effective in rapidly reversing VKA-associated coagulopathy; however, this protocol should be used cautiously in patients at high risk for thrombosis.

Prospective monitoring of plasma and platelet transfusions in a large teaching hospital results in significant cost reduction

BACKGROUND: Plasma and platelets (PLTs) are often transfused to correct mild to moderately abnormal laboratory values. Our objective was to reduce unnecessary plasma and PLT transfusions to nonbleeding patients by prospective triage and education of end users in evidence‐based hemostasis and transfusion medicine practices.

Role of ADAMTS13 in the management of thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP)

The clinical presentation of thrombotic thrombocytopenia purpura (TTP) and other thrombotic microangiopathies (TMAs) can often be similar. The role of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in diagnosing TTP is accepted by most researchers but continues to be debated in a few studies. We report the experience of our single‐centre academic institution, where ADAMTS13 is used to diagnose TTP and guide plasma exchange (PLEX). Patients presenting to our institution with thrombotic microangiopathy (60 patients) between January 2006 and December 2012 were divided into two groups based on ADAMTS13 activity and clinical history. Patients with ADAMTS13 activity <10% were included in the TTP (n = 30) cohort while patients with activity >11% were classified as ‘other microangiopathies’ (TMA, n = 30). PLEX was only initiated in patients with a high likelihood of TTP and discontinued when the baseline ADAMTS13 activity was >11%. Patients with severe ADAMTS13 deficiency (TTP group) showed significant presenting differences: lower platelet counts, less renal dysfunction, higher presence of neurological abnormalities, and greater haemolysis markers as compared to non‐deficient patients (TMA group). Most importantly, patients without severe ADAMTS13 deficiency were safely managed without increased mortality despite receiving no PLEX or discontinuing PLEX after a short course (upon availability of ADAMTS13 results). In conclusion, ADAMTS13 can be used to diagnose TTP and guide appropriate PLEX therapy.

Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia.

Objectives:  To correlate optical density and percent inhibition of a two‐step heparin‐induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration.

Advantages of isovolemic hemodilution‐red cell exchange therapy to prevent recurrent stroke in sickle cell anemia patients

Chronic simple hypertransfusion (every 3 to 4 weeks) effectively prevents secondary stroke in children with sickle cell anemia but leads to iron overload despite chelation therapy. Conventional red blood cell exchange (C‐RBCx) has advantages over simple transfusion: no net iron gain and less frequent hospital visits. However, C‐RBCx requires more red blood cell units, an apheresis instrument and skilled personnel; it is also more expensive. We developed a modified procedure where isovolemic hemodilution precedes RBCx (IHD‐RBCx) to decrease RBC units required and to increase the interval between procedures. Twenty patients underwent IHD‐RBCx over a period of 7 years. IHD‐RBCx required 11% fewer RBC units and increased inter‐procedure interval from 37 to 53 days compared to C‐RBCx. The median number of annual procedures decreased from 9.8 to 7.0 per patient, resulting in estimated savings of more than

Intravenous methylprednisolone versus therapeutic plasma exchange for treatment of anti-n-methyl-d-aspartate receptor antibody encephalitis: A retrospective review

4.5 million over 10 years for 20 patients while providing improved care. Five patients have discontinued chelation therapy; three while on C‐RBCx and two while on IHD‐RBCx. No adverse events occurred related to the isovolemic hemodilution phase and no patients had recurrent stroke. IHD‐RBCx is a safe, efficient, and cost effective therapy for secondary prevention of stroke in patients with sickle cell anemia. J. Clin. Apheresis, 2011.

Coagulation factor levels in neurosurgical patients with mild prolongation of prothrombin time: effect on plasma transfusion therapy

Introduction: Anti‐N‐methyl‐d‐aspartate (NMDA) receptor antibody encephalitis is an increasingly recognized form of autoimmune encephalitis. Conventional treatments include therapies such as corticosteroids, intravenous immunoglobulin (IVIg), and/or therapeutic plasma exchange (TPE). Although TPE is regularly used for treatment of anti‐NMDA receptor antibody encephalitis, the American Society for Apheresis has given it a category III recommendation only. Earlier administered immunotherapies in tumor‐negative patients may facilitate faster recoveries, but it remains unclear whether or not TPE is superior to steroids and/or IVIG. Methods: We retrospectively evaluated 10 of 14 patients that received steroids and TPE with modified Rankin scores and subjectively assessed the point of largest sustained improvement in all 14 patients. Results: In the patients that received both steroids and TPE at our institution during the same hospitalization (only 10 of 14 patients), 7/10 patients after TPE had improved with the modified Rankin score versus 3/10 patients after steroids. The average modified Rankin score improvement after steroids in this group was −0.1 as compared with 0.4 after TPE. Based on subjective chart review analysis during which all 14 patients were assessed, the largest sustained improvement occurred immediately following the third–fifth exchange in 9/14 patients, whereas only 2/14 patients appeared to have had significant benefit immediately following steroids. Conclusions: This is compelling preliminary data that suggests that corticosteroids may not be as effective compared to steroids followed by TPE. Given the importance of time‐sensitive treatment, more formal studies may illuminate the ideal first‐line treatment for anti‐NMDA receptor antibody encephalitis. J. Clin. Apheresis 30:212–216, 2015.

Is it quinine TTP/HUS or quinine TMA? ADAMTS13 levels and implications for therapy†

OBJECT Neurosurgical patients often have mildly prolonged prothrombin time (PT) or international normalized ratio (INR). In the absence of liver disease this mild prolongation appears to be due to the use of very sensitive PT reagents. Therefore, the authors performed relevant coagulation factor assays to assess coagulopathy in such patients. They also compared plasma transfusion practices in their hospital before and after the study. METHODS The authors tested 30 plasma specimens from 25 patients with an INR of 1.3-1.7 for coagulation factors II, VII, and VIII. They also evaluated plasma orders during the 5-month study period and compared them with similar poststudy periods following changes in plasma transfusion guidelines based on the study results. RESULTS At the time of plasma orders the median INR was 1.35 (range 1.3-1.7, normal reference range 0.9-1.2) with a corresponding median PT of 13.6 seconds (range 12.8-17.6 seconds). All partial thromboplastin times were normal (median 29.0 seconds, range 19.3-33.7 seconds). The median factor VII level was 57% (range 25%-124%), whereas the hemostatic levels recommended for major surgery are 15%-25%. Factors II and VIII levels were also within the hemostatic range (median 72% and 118%, respectively). Based on these scientific data, plasma transfusion guidelines were modified and resulted in a 75%-85% reduction in plasma orders for mildly prolonged INR over the next 2 years. CONCLUSIONS Neurosurgical patients with a mild prolongation of INR (up to 1.7) have hemostatically normal levels of important coagulation factors, and the authors recommend that plasma not be transfused to simply correct this abnormal laboratory value.

Bortezomib for chronic relapsing thrombotic thrombocytopenic purpura: A case report

Thrombocytopenia with or without microangiopathy following quinine is often referred to as quinine “hypersensitivity.” When schistocytes are present it is frequently termed “quinine‐associated TTP/HUS.” A severe deficiency of the vWF‐cleaving protease, ADAMTS13, is associated with idiopathic TTP. A previous study of patients with “quinine‐associated TTP/HUS” found that ADAMTS13 activities were not abnormal in 12/12 patients. A retrospective review of TTP patients with quinine‐associated thrombotic microangiopathy (TMA) for whom ADAMTS13 was measured before plasma exchange was performed. Six patients were identified. All were females (age range: 43 to 73, mean = 61.7 years) and had taken quinine for leg cramps. Four of the six experienced renal failure requiring dialysis. Five of the patients had D‐Dimers levels measured, all were elevated. In four patients the levels were ≥18 times the upper limit of normal. ADAMTS13 was normal in four patients and mildly decreased in two patients. We conclude that while thrombocytopenia and schistocytosis can be seen in quinine‐associated TTP/HUS, the pathophysiology seems to be distinct from that seen in most cases of idiopathic TTP (i.e., severely decreased ADAMTS13 with an inhibitor). We recommend that a TMA in association with quinine be consistently referred to as quinine‐associated thrombotic microangiopathy (quinine‐TMA) to better distinguish this entity from idiopathic TTP. The use of plasma exchange in quinine‐TMA is called into question. J. Clin. Apheresis, 2009.

Therapeutic plasma exchange in the management of sepsis and multiple organ dysfunction syndrome: A report of three cases

Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder characterized by a severe deficiency of ADAMTS13 activity. Although therapeutic plasma exchange (PLEX) is the standard of care, 30% to 50% patients develop exacerbation or relapse, requiring immunomodulatory agents. Of these agents, glucocorticoids, rituximab, and cyclosporine A are the most frequently used.