1. RBC transfusion does not increase risk of hypercoagulability and VTE.
   
2. RBC transfusion increases VTE risk in adults but not the pediatric patient population.
   
3. Patients who receive massive transfusion protocol have a decreased risk of VTE.
   
4. RBC transfusions have a dose‐response effect with increased risk of VTE at higher transfusion requirements.
   
5. RBC storage time prior to transfusion has no physiologic effects on VTE risk.

The risk of VTE in critically ill patients is increased in those receiving blood product transfusions. A recent meta‐analysis by Wang et al. that included more than 3.5 million patients found an odds ratio of 2.95 in development of VTE among patients who received preoperative blood transfusion compared to those who did not. An analysis by Goel et al. of the American College of Surgeons National Surgical Quality Improvement Program (ACS‐NSQIP) registry from 2014, including greater than 750,000 patients who received at least one perioperative RBC transfusion, found an association with RBC transfusion and VTE (OR 2.1), DVT (2.2), and PE (1.9) independent of other risk factors and across all surgical subspecialties analyzed. Additionally, a significant dose‐response effect was observed with increased odds of VTE as the number of RBC transfusion events increased – OR 2.1 for 1 event, OR 3.1 for 2 events, and OR 4.5 for 3 or more events compared to no intraoperative or postoperative RBC transfusions (p < 0.001 for trend). A similar increased VTE risk is seen in pediatric patients. A study of approximately 20 000 neonates, 80 000 infants, and 380 000 children found that VTE was significantly more common in all age groups – OR 4.1 in neonates, OR 2.4 in infants, and OR 2.2 in children. Weight‐based volume of RBCs transfused was associated with VTE in a dose‐dependent manner. Patients receiving massive fluid and blood product resuscitation after major hemorrhage due to trauma display a complex coagulation disorder that is multifactorial in nature. Coagulopathy is often perceived as hemorrhagic, but it is important to recognize that extensive hemodilution affects procoagulants, as well as anticoagulants, profibrinolytic, and antifibrinolytic elements. Studies on VTE risk in patients who survive MTP show an odds ratio of 2–3 compared to those who did not receive MTP. There are several effects of RBC storage that can increase the risk of VTE. Free hemoglobin from hemolyzed cells scavenge nitric oxide. Its decreased concentration leads to endothelial dysfunction and contributes to intravascular thrombosis.

Answer: D

Bradburn EH, Ho KM, Morgan ME, D’Andrea L, Vernon TM, Rogers FB . Massive transfusion protocol and subsequent development of venous thromboembolism: statewide analysis. The American Surgeon 2021; 87:15–20.

1. Guillotine above‐knee amputation
   
2. Common femoral vein thrombectomy
   
3. Placement of an inferior vena cava filter
   
4. Venography and catheter‐directed and/or mechanical thrombolysis
   
5. Systemic thrombolysis

Phlegmasia cerulea dolens is an uncommon complication of acute iliofemoral DVT that can result in loss of limb or life. Extreme venous hypertension leads to obstructed arterial flow and critical limb ischemia. It is characterized by marked swelling of the lower extremity with pain and cyanosis. Sensorimotor deficits soon follow if not recognized and treated promptly. Development of gangrene and necessity of amputation are unfortunately common in this disease process. It is seen most commonly in the 5th and 6th decades of life and in the left lower extremity due to compression of the left common iliac vein by the right common iliac artery. The immediate goals are bed rest, elevation of the affected extremity, and heparin administration followed by intervention to aggressively reduce the thrombus load and prevent further thrombus propagation. This can be accomplished via various techniques including catheter‐directed thrombolysis (CDT), pharmacomechanical thrombolysis (PMT), and open thrombectomy. There is no consensus on a management algorithm, but most authors suggest a graduated approach from endovascular to open surgical treatments based on the extent of acute ischemia. This patient has Rutherford class IIa acute ischemia with minimal sensory impairment and intact motor function. His limb is potentially salvageable with prompt therapy. Of note, he should be considered for fasciotomies given his ischemic time prior to presentation. Common femoral vein thrombectomy and immediate amputation should be reserved for more extensive sensorimotor deficits and unsalvageable limbs, respectively. CDT has not been shown to increase the rate of embolization, so empiric IVC filter placement is not routine practice.

Answer: D

Broderick C, Watson L, Armon MP . Thrombolytic strategies versus standard anticoagulation for acute deep vein thrombosis of the lower limb. Cochrane Database of Systematic Reviews. 2021; 19;1:CD002783.

Chinsakchai K, Ten Duis K, Moll FL, de Borst GJ . Trends in management of phlegmasia cerulea dolens. Vascular and Endovascular Surgery 2011; 45:5–14.

Fleck D, Albadawi H, Shamoun F, Knuttinen G, Naidu S, Oklu R . Catheter‐directed thrombolysis of deep vein thrombosis: literature review and practice considerations. Cardiovascular and Diagnosis Therapy 2017; 7(Suppl 3):S228–S237.

Pouncey AL, Gwozdz AM, Johnson OW, Silickas J, Saha P, Thulasidasan N, Karunanithy N, Cohen AT, Black SA . AngioJet pharmacomechanical thrombectomy and catheter directed thrombolysis vs. catheter directed thrombolysis alone for the treatment of iliofemoral deep vein thrombosis: a single centre retrospective cohort study. European Journal of Vascular and Endovascular Surgery 2020; 60:578–585.

1. Women have a 4‐ to 5‐fold increase in venous thromboembolism risk during pregnancy and the postpartum period.
   
2. DVT occurs with equal frequency in each trimester and the postpartum period.
   
3. PE is more common during pregnancy than the postpartum period.
   
4. During pregnancy, 80–90% of DVTs occur in the left lower extremity.
   
5. VTE accounts for approximately 10% of all maternal deaths.

VTE complicates 0.5–3.0 per 1000 pregnancies and is the leading cause of maternal mortality in the United States. All of the factors in Virchow’s Triad (hypercoagulability, vascular injury, and venous stasis) occur in pregnancy. Pregnant or postpartum women carry a relative risk of 4.3 for VTE compared to nonpregnant women. Cesarean delivery also significantly increases risk of VTE compared to vaginal delivery with an odds ratio of 13.3. DVT occurs with equal frequency in each trimester and the postpartum period. The vast majority of DVTs in pregnancy occur in the left lower extremity, which accounts for 80–90% of cases. Of those, approximately 70% occur in the iliofemoral distribution, which are more prone to embolization. In nonpregnant patients, left lower extremity DVTs account for 55% of cases with 10% in the iliofemoral vein. DVT and PE during pregnancy or the postpartum period require anticoagulation similar to the general population. Unfractionated heparin (UFH) and low‐molecular‐weight heparin (LMWH) are safe during pregnancy with LMWH replacing UFH as the therapy of choice due to minimal excretion in breast milk and lower rates of adverse events (heparin‐induced thrombocytopenia, symptomatic osteoporosis, bleeding, and allergic reactions). Warfarin is contraindicated during pregnancy due to teratogenicity.

Answer: C

Blanco‐Molina A, Trujillo‐Santos J, Criado J, et al., for the RIETE Investigators. Venous thromboembolism during pregnancy or postpartum: findings from the RIETE Registry. Thrombosis and Haemostasis 2007; 97:186–190.

Creanga AA, Syverson C, Seed K, Callaghan WM . Pregnancy‐related mortality in the United States, 2011–2013. Obstetrics and Gynecology 2017; 130:366–373.

Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJIII . Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30‐year population‐based study. Annals of Internal Medicine 2005; 143:697–706.

Pomp ER, Lenselink AM, Rosendaal FR, Doggen CJ . Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. Journal of Thrombosis and Haemostasis 2008; 6:632–637.

1. Patients under age 18 should not receive chemical DVT prophylaxis.
   
2. The patient should be started on chemical prophylaxis with low‐molecular‐weight heparin every 12 hours.
   
3. Patients with an Injury Severity Score (ISS) ≥ 10 should receive chemical DVT prophylaxis.
   
4. The patient should have intermittent pneumatic compression devices (IPCs) and graduated compression stockings (GCSs) placed for VTE risk management.
   
5. The patient should receive active surveillance with DVT ultrasound in lieu of chemical DVT prophylaxis.

Prepubertal patients are generally a low‐risk population for VTE, a phenomenon thought to be due to a lack of sex hormones. Older children and adolescents have a VTE risk that approaches their adult counterparts. The Pediatric Trauma Society and the Eastern Association for the Surgery of Trauma joint practice management guideline recommend pharmacologic prophylaxis be considered for children older than 15 years of age and younger in postpubertal children with an Injury Severity Score greater than 25. Particular injury patterns that are high risk for VTE (i.e. pelvic fracture, long bone fracture, TBI) should be given consideration as well. Intermittent pneumatic compression devices and graduated compression stockings should be placed for mechanical VTE prophylaxis in the absence of an injury pattern contraindication. Several studies have investigated serial ultrasound surveillance in the absence of chemical VTE prophylaxis with no identified clinical benefit.

Answer: B

Landisch RM, Hanson SJ, Cassidy LD, Braun K, Punzalan RC, Gourlay DM . Evaluation of guidelines for injured children at high risk for venous thromboembolism: a prospective observational study. Journal of Trauma and Acute Care Surgery 2017; 82(5):836–844.

Liras IN, Rahbar E, Harting MT, Holcomb JB, Cotton BA . When children become adults and adults become most hypercoagulable after trauma: an assessment of admission hypercoagulability by rapid thrombelastography and venous thromboembolic risk. Journal of Trauma and Acute Care Surgery 2016; 80(5):778–782.

1. The effects of LMWH are more unpredictable than natural or unfractionated heparin (UFH).
   
2. The incidence of heparin‐induced thrombocytopenia is approximately 5% with LMWH compared to 1% with UFH.
   
3. The therapeutic effect of LMWH can be measured with the partial thromboplastin time (PTT), activating clotting time (ACT), or anti‐factor Xa assay.
   
4. LMWH is contraindicated in patients with a GFR 30–50 mL/min due to its renal clearance.
   
5. The risk of heparin‐induced thrombocytopenia is reduced with fondaparinux due to its lack of affinity for platelet factor 4.

Unfractionated heparin (UFH) consists of multiple molecular chains of various lengths and molecular weights. Low‐molecular‐weight heparin (LMWH) have only short chains with the class of drug being obtained by fractionation or depolymerization of UFH. Due to the lower degree of variation, the effects of LMWH are more predictable than UFH. LMWH also has a lower risk of heparin‐induced thrombocytopenia (HIT) at 1% compared to 5% with UFH. The effects of LMWH cannot be measured using PTT or ACT, but rather with an anti‐Xa level. Recent studies suggest that anti‐Xa monitoring for therapeutic levels is beneficial, particularly in patients at the extremes of weight. Also, many patients are subtherapeutic at the standard dosing of LMWH common in many institutions. LMWHs are contraindicated in severe renal impairment – defined by a creatinine clearance (CrCl) < 30 mL/min – due to their renal metabolism. There are no dose adjustments required in normal renal function (CrCl ≥ 80 mL/min), mild renal impairment (CrCl 50–79 mL/min) or moderate renal impairment (CrCl 30–49 mL/min).

Answer: E

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