Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin-induced thrombocytopenia: A systematic review.

BACKGROUND: Immunomodulatory strategies in heparin-induced thrombocytopenia (HIT) include the use of intravenous immune globulin (IVIG) and therapeutic plasma exchange (TPE). The optimal application of these therapies is unknown and outcomes data are limited. We investigated treatment categories and laboratory and clinical outcomes of IVIG and/or TPE in HIT with a systematic literature review. STUDY DESIGN AND METHODS: We searched MEDLINE, Embase, and Web of Science through December 2019 for studies combining controlled vocabulary and keywords related to thrombocytopenia, heparin, TPE, and IVIG. The primary outcome was treatment indication. Secondary outcomes were platelet recovery, HIT laboratory parameters, heparin re-exposure, and post-treatment course. Case-level data were analyzed by qualitative synthesis. RESULTS: After 4241 references were screened, we identified 60 studies with four main categories of IVIG and/or TPE use as follows: (a) treatment of refractory HIT (n = 35; 31%); (b) initial therapy (n = 45; 40%); (c) cardiopulmonary bypass surgery (CPB; n = 30; 27%); and (d) other (n = 2; 2%). IVIG was most commonly used for the treatment of refractory HIT while TPE was primarily used to facilitate heparin exposure during CPB. Both IVIG and TPE were equally used as initial therapy. Heparin re-exposure occurred without thrombotic event in 29 TPE-treated patients and three IVIG-treated patients. CONCLUSION: In patients with HIT, both TPE and IVIG are used for initial therapy or treatment of refractory HIT. However, TPE is more commonly used in patients undergoing CPB. Prospective studies may help clarify which treatment is indicated in HIT population subsets.

Alternatives to Transfusion.

OBJECTIVES: We discuss two main categories of blood substitutes: perfluorocarbons and hemoglobin-based oxygen carriers. METHODS: We provide a review of the notable products developed in both categories and include their attributes as well as their setbacks. RESULTS: We contribute a case report tothe growing literature of the successful use of Sanguinate. CONCLUSIONS: We find that artificial oxygen carriers are an attractive field of research because of the practical limitations and the multitude of potential complications that surround human blood transfusions.

Hemostasis testing and therapeutic plasma exchange: Results of a practice survey.

INTRODUCTION: Performing therapeutic plasma exchange (TPE) with albumin replacement decreases coagulation factor and platelet levels. No defined guidelines exist regarding laboratory testing to assess hemostasis in patients undergoing TPE. MATERIALS AND METHODS: A survey to evaluate hemostasis testing with TPE was distributed using online survey software. One response per institution was analyzed based on a hierarchical algorithm, excluding membrane filtration users, resulting in a maximum of 120 respondents per question. Descriptive analysis was performed with results reported as the number and/or frequency (%) of respondents to each question. RESULTS: The practices represented vary by institution type, number of apheresis procedures per year, and performance of TPE on children. Prior to TPE planned with albumin replacement, many respondents obtain laboratory studies for almost all patients (54.9% outpatients and 68.7% inpatients); however, some do not routinely obtain laboratory studies (9.7% outpatients and 4.4% inpatients). Hemoglobin/hematocrit, platelet count, fibrinogen, partial thromboplastin time (aPTT), and international normalized ratio (INR) are obtained prior to all TPE by 62.5%, 53.4%, 31.0%, 18.1%, and 17.7% of respondents, respectively; however, 1.0%, 8.7%, 29.0%, 38.3%, and 35.4%, respectively, do not routinely obtain these studies. Variation was observed in laboratory threshold values for action; the most common reported were hemoglobin/hematocrit <7 g/dL or 21% (31.0%), platelet count <50 × 109 /L (24.1%), fibrinogen <100 mg/dL (65.3%), aPTT >reference range and >1.5 times reference range (tied, 28.1%), and INR >1.5 (20.7%). CONCLUSIONS: Practice variation exists in hemostasis laboratory testing and threshold values for action with TPE. Further studies are needed to determine optimal hemostasis testing strategies with TPE.

Experience with uncrossmatched blood refrigerator in emergency department.

BACKGROUND: Uncrossmatched packed red blood cell (PRBC) transfusion is fundamental in resuscitation of hemorrhagic shock. Ready availability of uncrossmatched blood can be achieved by storing uncrossmatched blood in a blood bank refrigerator in the emergency department (ED), but could theoretically lead to inappropriate uncrossmatched use. METHODS: This retrospective study was performed at a level I trauma center from January 2013 to March 2014. Possibly inappropriate transfusion was defined as patients who received at least one unit of blood from the ED refrigerator and no more than two units of PRBC in the first 24 hours. Deaths within the first 24 hours were excluded. Patients who received blood from the ED refrigerator who received ≤2 units total in 24 hours were compared with those who received >2 units. RESULTS: 158 adults received blood from the ED refrigerator. 140 (88.6%) were trauma patients. 37 (23.4%) received massive transfusion (MT). 42 (26.6%) deaths were excluded. 29 patients received ≤2 units and 87 received >2 units in the first 24 hours. The ≤2 units group had a higher systolic blood pressure (116 mm Hg vs. 102 mm Hg, p=0.042), lower base deficit (6.4 mEq/L vs. 9.4 mEq/L, p=0.032), higher hematocrit (34% vs. 30%, p=0.024), lower rate of MT protocol activation (27.6% vs. 58.6%, p=0.005), and lower rates of transfusion of fresh frozen plasma (17.2% vs. 54.0%, p=0.001) and platelets (13.8% vs. 39.1%, p=0.012). Appropriately transfused patients were more likely to have evidence of shock with active, non-compressible hemorrhage. Potentially inappropriate uses were more likely in patients either without evidence of hemorrhage or without signs of shock. DISCUSSION: Storing uncrossmatched blood in the ED is an effective way to get PRBCs transfused quickly in hemorrhaging patients and is associated with a low rate of unnecessary uncrossmatched transfusion. Provider education and good clinical judgment are imperative to prevent unnecessary use. LEVEL OF EVIDENCE: Level III, therapeutic.

Hemostasis management and therapeutic plasma exchange: Results of a practice survey.

BACKGROUND: Patients undergoing therapeutic plasma exchange (TPE) may present with risks for hemorrhage or thrombosis. Use of replacement fluids devoid of coagulation factors will decrease factor levels and platelet levels. There are no established guidelines for hemostasis management in these situations. MATERIALS AND METHODS: A survey to evaluate current hemostasis management practice during TPE was conducted using online survey software. One response per institution was analyzed based on a hierarchical algorithm, excluding membrane filtration users, resulting in a maximum of 107 respondents. Descriptive analysis was performed with results reported as the number and frequency (%) of respondents to each question. RESULTS: Apheresis Medicine physicians, alone (59.4%) or jointly with the requesting provider (29.2%), choose the replacement fluid. Based on a theoretical patient case receiving five TPEs approximately every other day, the percent of respondents who would use albumin with or without normal saline was 94.7% with no history of a bleeding or clotting disorder, 1.1% with active bleeding, and 8.8% with hypofibrinogenemia (<100 mg/dL) due to recent TPE. More respondents would use albumin with or without normal saline for replacement fluid when a minor invasive procedure (49.5%) vs a major surgery (8.9%) was performed 1 day before TPE. Replacement fluid selection varied among respondents for several other clinical conditions. The most frequent use for cryoprecipitate by respondents (14.3%) was hypofibrinogenemia. CONCLUSIONS: These survey results demonstrate wide interinstitutional variation in replacement fluid selection to manage hemostasis in patients undergoing TPE. Further studies are needed to guide optimal hemostasis management with TPE.

Disseminated Intravascular Coagulation.

OBJECTIVES: To provide a review of the definition, pathophysiology, differential diagnosis, and treatment of disseminated intravascular coagulation (DIC). METHODS: A case scenario and a review of the literature related to the pertinent facts concerning DIC are provided. RESULTS: DIC is a systemic pathophysiologic process and not a single disease entity, resulting from an overwhelming activation of coagulation that consumes platelets and coagulation factors and causes microvascular fibrin thrombi, which can result in multiorgan dysfunction syndrome from tissue ischemia. Some conditions associated with acute DIC include septic shock, exsanguinating trauma, burns, or acute promyelocytic leukemia. CONCLUSIONS: The massive tissue factor stimulus results in excess intravascular thrombin, which overcomes the anticoagulant systems and leads to thrombosis. Because of consumption of coagulation factors and platelets, DIC also has a hemorrhagic phase. Treatment of the bleeding patient with DIC is supportive with the use of blood components.

How do I implement a more restrictive transfusion trigger of hemoglobin level of 7 g/dL at my hospital?

BACKGROUND: The red blood cell (RBC) transfusion trigger is a major driver of transfusion practice and affects health care costs and in some instances patient outcomes. Reducing the transfusion threshold will decrease RBC utilization and hospital costs. STUDY DESIGN AND METHODS: The hospital transfusion committee, endorsed by the medical staff executive committee, developed an educational program for physicians, nurses, and blood bank staff focusing on the scientific basis for a transfusion trigger of hemoglobin (Hb) of 7 g/dL rather than 8 g/dL as well as a program to discourage the routine 2-unit RBC transfusion. RBC transfusion practice review was performed and those physicians transfusing outside of the new variables were questioned as to the necessity for the transfusion. RESULTS: A total of 4492 RBC units were saved and 662 patients were not transfused over the three fiscal years (FYs), 2010, 2011, and 2012, compared to 2009 baseline. Direct cost savings over 3 years with a transfusion trigger of Hb of 7 g/dL was $943,320. If activity-based costing is used, the savings may have reached as high as $5,314,036. The number of single-unit RBC transfusions increased steadily over the course of the study while the number of 2-unit transfusions remained relatively stable over the three FYs 2010 to 2012. CONCLUSION: A Hb level of 7 g/dL is the transfusion threshold which is being adopted by many hospitals. Institutional culture change to a Hb level of 7 g/dL can be implemented with the right champion when endorsed by upper echelon medical leadership and hospital administration.

Consensus review of the treatment of cardiovascular disease in people with hemophilia A and B.

With advances in care, increasing numbers of people with hemophilia (PWH) achieve near-normal life expectancies and present with typical age-related cardiovascular conditions. Evidence-based guidelines for medical or surgical management of cardiovascular conditions in individuals with hemophilia are limited. Published recommendations exist for the management of some common cardiovascular conditions (eg, ischemic heart disease, atrial fibrillation), but identifying optimal strategies for anticoagulant or antithrombotic therapy constitutes the primary challenge of managing nonoperative cardiovascular disease (CVD) in PWH. In general, as long as factor concentrates or other hemostatic therapies maintain adequate hemostasis, the recommended medical and surgical management of CVD in PWH parallels that in individuals without hemophilia. The presence of factor inhibitors complicates hemophilia management. Published outcomes of CVD treatment in PWH are similar to those in the general population. Specific knowledge about factor replacement, factor inhibitors, and disease-specific treatment distinguishes the cardiovascular care of PWH from similar care of individuals without this rare bleeding disorder. Furthermore, a multidisciplinary approach incorporating a hematologist with an onsite coagulation laboratory, ideally associated with a hemophilia treatment center, is integral to the management of CVD in PWH.

Comparison of outcomes of group O vs non-group O premature neonates receiving group O RBC transfusions.

OBJECTIVES: At some institutions all infants requiring RBC transfusions in neonatal intensive care units (NICUs) receive only group O RBCs. Although transfused group O plasma is minimized in packed RBCs, small amounts of residual anti-A, anti-B, and anti-A,B in group O packed RBCs may bind to the corresponding A and B antigens of non-group O RBCs, possibly hemolyzing their native RBCs and thereby releasing free hemoglobin, theoretically resulting in hypercoagulability and promoting bacterial growth from free iron. METHODS: Premature infants in the University of Kentucky Children's Hospital NICU database who were transfused (all received group O transfusions) were compared for a number of severity markers to determine if non-group O patients had worse outcomes than group O patients. RESULTS: In this NICU sample, 724 neonates received at least 1 blood component. No significant differences were found between group O and non-group O infants with regard to final disposition or complications. CONCLUSIONS: This reassuring finding validates the longstanding neonatal transfusion practice of using group O packed RBCs for infants of all blood groups in the NICU. However, a recent study shows increased mortality from necrotizing enterocolitis in group AB neonates at a facility transfusing only group O RBCs to neonates of all blood groups and suggests a change in neonatal transfusion practice to ABO group-specific RBCs; therefore more studies may be warranted.

Initial results of a structured rotation in hematology and transfusion medicine for anesthesiology residents.

STUDY OBJECTIVE: To develop and evaluate a new curriculum in transfusion medicine for anesthesiology residents. STUDY DESIGN: Quasi-experimental study. SETTING: Single center, pilot curriculum in the anesthesiology residency program at a university-affiliated medical center. PARTICIPANTS: Group TM consisted of residents who participated in the one month-long transfusion medicine rotation in postgraduate year 2 (PGY2; n = 9). The comparison group (non-TM) consisted of residents who had no exposure to the transfusion medicine rotation (n = 21). MEASUREMENTS: We compared results of the 2009 American Board of Anesthesiology In-Training Exam (ABA-ITE) 2009 by residents of our program with the national performance of residents in the first clinical anesthesia year (AMG CA1 = PGY-2) and second clinical anesthesia year (AMG CA2 = PGY-3) on transfusion medicine/hematology knowledge. Performance on a pre-test and post-test of those who took part in the transfusion medicine curriculum, and overall performance on the ABA-ITE, of departmental residents who had and had not participated in the Transfusion Medicine curriculum within the target knowledge area of hematology/transfusion medicine and compared against national peer performance data, was assessed. An anonymous electronic survey (5-Point Likert scale) was used to assess the perceived educational value of the curriculum. MAIN RESULTS: Transfusion medicine-related knowledge of anesthesia residents markedly improved from the pre- to post-rotation examination and on the ABA-ITE. In the ABA-ITE 2009, the TM group performed better than their national peers (AMG CA1 and CA2) in the hematology content area. The post-rotation anonymous resident survey indicated high resident satisfaction. CONCLUSIONS: A structured transfusion medicine curriculum improved anesthesiology resident knowledge in transfusion medicine and was associated with high learner satisfaction.

Transfusions in burn patients with/without comorbidities.

Medical comorbidities such as renal, cardiac, and cerebrovascular disease are known risk factors for mortality in burn patients. Patients with large burns often require blood transfusions during excision and skin grafting. The purpose of this study was to determine if there was a difference in the transfusion requirements of burn patients with/without comorbidities. This was a retrospective review of burn patient data between March 1999 and May 2004. There were 1,615 admissions to the burn unit; comorbidity data was available on 1,490 patients. Of these, 383/1,490 (26%) had comorbid conditions upon admission: 85/383 (22%) were transfused; 52/85 (61%) also underwent skin grafting. Most patients (298/383) with comorbidities were not transfused; however, 108/298 (36%) were grafted. Transfused patients with comorbidities had a mean +/- SD age of 53 +/- 18 years old, a 19% +/- 22% TBSA burn, and a length of stay of 29 +/- 26 days compared with patients with comorbidities who did not require transfusion and were 48 +/- 19 years old, had 8 +/- 13% TBSA, and a length of stay of 8 +/- 8 days. Of patients with comorbidities, 31/54 (57%) were transfused in the <10% TBSA group and 26/44 (59%) in the 10 to 19% TBSA group. There was a 5-fold increase in mortality among the transfused patients with comorbidities compared with the nontransfused group. Patients with comorbidities were more likely to be transfused in the <20% TBSA patient group. The odds of receiving a transfusion were highest in patients with cardiac diseases, stroke, and other central nervous system and psychiatric disorders. Co-occurring conditions that increased the odds of receiving a transfusion were procedures and inhalation with burn injury.

Use of blood bank services in a burn unit.

Burn patients may need transfusions, especially during surgery. The purpose of the study was to determine blood bank services utilization at an urban burn center. This was a retrospective review (March 1999 to May 2004) of burn patient data on blood utilization. There were 1615 admissions; 800 (49.5%) of the patients had a type and screen (T and S); 180 of 1615 (11%) were transfused with 1691 red blood cell (RBC) units; 616 units of fresh- frozen plasma (FFP), 399 units of pooled platelets, and 38 units of apheresis platelets. Of the 180 transfused patients, 140 (79%) received RBCs, 11 (6%) received RBCs plus FFP, 23 (13%) received RBCs plus FFP plus platelets, and 3 (2%) each received RBCs plus platelets and FFP. Overall, 3393 red cell units were cross-matched, and 1691 units were transfused for a cross-match/transfused unit (C/T) ratio of 2.01. Seventy-three (5.7%) of 1282 of patients with 0% to 10% TBSA required transfusions; 42 (21%) of 193 with 11% to 20% TBSA; 24 (39%) of 61 with 21% to 30% TBSA; and 62% of patients with 31% or greater TBSA required transfusion (P = .001). As %TBSA increased, more of the cross-matched units were transfused: 37% in the 0% to 10% TBSA to 59% in the 30% or greater TBSA burn. The C/T ratio in the 0% to 10% TBSA was 2.69; only 18% of patients with a T&S received blood. Although most patients who underwent transfusion were in the less than 30% TBSA group, more of the red cell units were used in patients with a 30% or greater TBSA burn. Elimination of admission T&S and cross matches in burn patients with less than 20% TBSA may improve the C/T ratio in this cohort.