Prophylactic Low Molecular Weight Heparin Research Articles

Fat Embolism Syndrome from Bone Marrow Necrosis Following Peg-Filgrastim in a Patient with Primary Mediastinal B-Cell Lymphoma

Background: The mechanism of atraumatic fat embolization syndrome (FES) is poorly understood. However, mechanical and biochemical processes are the two plausible theories that exist. FES from bone marrow necrosis caused by hemoglobinopathies, use of chemotherapy in hematopoietic malignancies and from use of G-CSF has been reported. In our case, a young male patient with primary mediastinal large B-cell lymphoma presented with microhemorrhages and punctiform ischemic brain lesions after receiving chemoimmunotherapy and pegylated G-CSF. Case: A 29-year-old male recently diagnosed with primary mediastinal large B-cell lymphoma presented to our ED with severe bone pain after receiving his first cycle etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin, and rituximab (DA R-EPOCH) with peg-filgrastim support. He was discharged with pain control and subsequently received his second cycle of DA-R-EPOCH (20% increase in etoposide, doxorubicin, and cyclophosphamide) with a retrial of peg-filgrastim. His WBC count rose to a peak of 41,100K/UL on the seventh day of his second cycle. Ten days after receipt of his 2 nd peg-filgrastim, he presented to the ED with complaints of generalized weakness, decreased oral intake and mild imbalance with his gait. His blood pressure was 103/71 mmHg, heart rate was 138 beats per minute, respiratory rate was 22 breaths per minute and oxygen saturation was 91% on room air; and he required 2 liters of supplemental oxygen. Laboratory studies showed Hb of 8.1 gm/dL, PLT of 47,000k/UL and WBC of 10,100k/UL. The WBC differential was consistent with myeloid predominance with a left shift and some enucleated RBC consistent with use of peg- filgrastim. LDH was 2874 U/L, albumin was 3.8 g/L, PTT 23.1 seconds, PT 13.8 seconds, INR 1.2. A CT with angiography of the chest showed no pulmonary embolism but an anterior mediastinal soft tissue mass, which decreased in size compared to his prior image, with erosive changes of sternum. Mediastinal and axillary lymphadenopathy also overall decreased in size. Due to developing confusion and mild left-sided facial weakness, MRI with and without intravenous contrast of the brain demonstrated numerous petechial microhemorrhages throughout the brain parenchyma in the supratentorial compartment and posterior cranial fossa with involvement of superficial and deep parenchymal regions. Many were seen clustered in the internal/external watershed regions. Transthoracic echocardiogram with bubble study demonstrated a patent foramen ovale (PFO). Prophylactic low molecular weight heparin was started and he was discharged after improvement of symptoms. He proceeded to complete 4 more cycles of standard dose R-EPOCH with prophylactic levofloxacin instead of peg-GCSF. His neurologic symptoms resolved and did not recur. Conclusion: This case highlights a rare but severe complication of BMN causing fat embolization syndrome in a patient receiving G-CSF following R-EPOCH for high PMBCL with sternal bone involvement. We hypothesize that the rapid proliferation of myeloid cell lines induced by G-CSF led to vascular occlusion and relative hypoxemia. Furthermore, the prolonged incorporation of corticosteroids is known to cause adipose tissue disruption. His underlying disease involved invasion into his sternum which further would support the theory of bone marrow necrosis being able to dislodge into the vasculature. This case is important to alert physicians to be cognizant of this severe complication and to provide some evidence for continuing curative intent treatment with the omission of G-CSF support.

CDKN2C Deletion on 1p32 Locus As Part of Irwazh Score, a New Risk Assessment Model for Venous Thromboembolism Occurring within 6-12 Months of Treatment Initiation in Newly Diagnosed Multiple Myeloma

Background Adequate risk-stratification of venous thromboembolism (VTE) in multiple myeloma (MM) is an unmet need. Methods This is a retrospective study of 320 newly diagnosed MM (NDMM) patients treated from 2011 to 2023. All gave their informed consent. Required minimal follow-up (FU) length was 12 months or lower if VTE or death occurred. We aimed to evaluate VTE incidence at 6 and 12 months of first line treatment (L1) initiation, identify risk predictors and assess VTE impact on overall survival (OS). Comorbidities, baseline demographic (excluding race), clinical, biological (including FISH) and imaging data, treatment exposures, response profile and OS were all analyzed. Total scores for 4 existing risk assessment models (RAM) (IMPEDE-VTE, SAVED, PRISM, IFM/DFCI-related) were also calculated from L1 start. VTE events (VTEe) were adjudicated to exclude superficial ones and restrict analysis to documented deep vein thrombosis (DVT) and pulmonary embolism (PE). Predictors validated by Cox model were weighted based on their hazard ratios (HR). Results The cohort comprised 147 (45.9%) women and 111 (34.7%) transplant-eligible patients. Overall median age was 70.1 (36.6-98.4) years and 205 (64.1%) subjects were >65. Two hundred and twenty-five (70.3%) received standard-of-care regimens containing immunomodulatory drugs (IMID) (Thalidomide in 98: 30.6%; Revlimid in 127: 39.7%), while 130 (40.6%) received high-dose (≥160 mg) Dexamethasone (HDD) per L1 cycle. VTE prophylaxis was omitted in 32 (10%) or consisted of NSAID in 97 (30.3%), prophylactic low molecular weight heparin (LMWHp) in 115 (36%) and direct oral anticoagulant (DOA) in 55 (17.2%), while 10 (3.1%), 9 (2.8%) and 2 (0.6%) were previously receiving curative LMWH (LMWHc), vitamin K antagonist (VKA) or a mixed regimen, respectively, for prior VTE or other indications. In 33 (10.3%) patients, 34 VTEe occurred (31 [91.2%] within the first 6 months): 4 (11.8%) as both PE and DVT; 3 (8.8%) as PE; 27 (79.4%) as isolated proximal (12 [35.3%]) or distal (15 [44.1%]) DVT of the upper (2 [5.9%]) or lower (25 [73.5%]) limbs, including 3 (8.8%) with both proximal and distal and 3 (8.8%) close to central venous catheter. Based on Cox univariate analysis, VTEe were not related to usual parameters such as past VTE history, IMID, HDD or EPO exposure, prophylaxis omission or modality or recent surgery. A 6-parameter RAM, named Irwazh score, was built from multivariate Cox model, including: age <55 years (HR 0.34; 95% confidence interval [CI]: 0.0-0.8; p=0.014), prior diabetes (HR 3.41; 95% CI: 1.48-7.85; p=0.004), creatinine clearance (Cr-Cl) using MDRD <40 ml/mn (HR 2.64; 95% CI: 1.26-5.51; p=0.009), CRP ≥10 mg/dl (HR 2.65; 95% CI: 1.27-5.48; p=0.009), ≥50% 1p32 deletion (HR 3.44; 95% CI: 1.17-10.09; p=0.024) and minimal response (MR) to L1 (HR 4.67; 95% CI: 1.71-12.73; p=0.003). Area under the curve (AUC) was 0.718 (95% CI: 0.624-0.811; p<0.0001) at 12 months and 0.731 (95% CI: 0.636-0.825; p<0.0001) at 6. In comparison, AUC was 0.649 (95% CI: 0.546-0.751; p=0.004) for IMPEDE-VTE, 0.597 (95% CI: 0.505-0.689; p=0.039) for PRISM, 0.584 (95% CI: 0.486-0.682: p=0.091) for IFM/DFCI-related and 0.580 (95% CI: 0.473-0.687; p=0.141) for SAVED (Figure 1). Based on points attributed to each parameter (age <55 years: 1; prior diabetes: 9; Cr-Cl<40 ml/mn: 6; CRP≥10 mg/dl: 6; ≥50% 1p32 deletion: 9; MR: 11), patients were stratified into low (<6 points), intermediate (6-15) and high risk (≥16), with 12-month cumulative VTE incidence of 4,51% (6/133), 10,45% (16/153) and 35,29% (12/34), respectively. Of low-risk patients, 2 were receiving NSAID and 4 LMWHp; of intermediate-risk ones, 2 had no prophylaxis, 9 were under NSAID and 5 LMWHp; of high-risk ones, 2 had no prophylaxis, 5 were receiving NSAID, 2 LMWHp, 1 VKA, 1 LMWHc and 1 DOA. Using Kaplan-Meier analysis for VTE-free survival, statistical difference was found significant between low- and intermediate-risk ( p=0.043), low- and high-risk ( p<0.0001) and intermediate- and high-risk groups ( p=0.000) (Figure 2). Median total FU was 33.2 (0.2-147) months; OS assessment using Cox model did not find a significant statistical impact of VTE neither at 6 ( p=0.491) and 12 ( p=0.199) months nor during the whole FU length ( p=0.438). Conclusion The Irwazh score, with an unprecedented FISH feature, a statistically significant risk-stratifying power and a better AUC than existing VTE RAMs is worth validating in a larger clinical study.

236 The Hypercoagulable State in COVID-19 and Implications for Free Flap Surgery in the Lower Limb

Abstract Aim COVID-19 associated coagulopathy is widely documented in severe COVID-19 infection and COVID-19 Vaccine-Induced Thrombotic Thrombocytopaenia. However, much of this evidence relates to macrovascular thrombosis with limited evidence on the impact of previous mild, asymptomatic COVID-19 infection, or vaccination on microvascular thrombosis in free tissue transfer. We compared the rate of thrombotic complications in traumatic lower limb injuries requiring free flap reconstruction in the pre- and post-COVID era. Method Adult patients undergoing lower limb free flap reconstruction were identified at a single centre over two three-month periods (2019 and 2021). Standard thromboprophylaxis was used for all patients (intraoperative intermittent pressure devices, post-operative thromboembolic deterrent stockings, and prophylactic low molecular weight heparin until discharge). Thrombotic complications were recorded and compared using a chi-squared test. Results In the pre-COVID cohort, 51 patients underwent 52 free flaps. One flap (1.9%) suffered anastomotic thrombosis resulting in flap compromise. Post-COVID, 39 patients underwent 43 free flaps. Nine flaps suffered anastomotic thrombosis (21%) and one patient suffered a pulmonary embolus. This increase was statistically significant (p = 0.002). In the post-COVID cohort, four patients had a COVID-19 infection and 25 patients (64%) had at least one dose of a COVID-19 vaccine before free flap surgery. No patients had an active COVID-19 infection on admission. Conclusions In the post-COVID era there was an increased rate of thrombotic complications in lower limb free flap patients. Further research is required to delineate the best course of action when planning free tissue transfer for patients who have had previous COVID-19 infection or vaccination.

Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India.

Patients admitted to intensive care units (ICUs) with severe coronavirus disease (COVID-19) are associated with high mortality. The present retrospective, multicenter study describes the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian Council of Medical Research (ICMR), India. Prospectively collected data from participating institutions were entered into the electronic National Clinical Registry of COVID-19. We enrolled patients aged >18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative in RT-PCR report, death within 24 hours of ICU admission, or incomplete data. Their demographic and laboratory variables, ICU severity indices, treatment strategies, and outcomes were analyzed. A total of 5,865 patients were enrolled. Overall mortality was 43.2%. Non-survivors were older (58.2 ± 15.4 vs 53.6 ± 14.7 years; p = 0.001), had multiple comorbidities (33.2% vs 29.5%, p = 0.001), had higher median D-dimer (1.56 vs 1.37, p = 0.015), higher CT severity index (16.8 ± 5.2 vs 13.5 ± 5.47, p = 0.001) and longer median hospital stay (10 vs 8 days, p = 0.001) and ICU stay (5 vs 4 days, p = 0.001), compared with survivors.On multivariate analysis, high CRP (HR 1.008, 95% CI: 1.006-1.010, p = 0.001) and high D-dimer (HR 1.089, 95% CI: 1.065-1.113, p < 0.001) were associated with invasive mechanical ventilation while older age (HR 1.19, CI: 1.001-1.038, p = 0.039) and high D-dimer (HR-1.121, CI: 1.072-1.172, p = 0.001) were independently associated with mortality and while the use of prophylactic low molecular weight heparin (LMWH) (HR 0.647, CI: 0.527-0.794, p = 0.001) lowered mortality. Among 5,865 COVID-19 patients admitted to ICU, mortality was 43.5%. High CRP and D-dimers were independently associated with the need for invasive mechanical ventilation while older age and high D-dimer were associated with higher mortality. The use of prophylactic LMWH independently reduced mortality. Kajal K, Singla K, Puri GD, Bhalla A, Mukherjee A, Kumar G, et al. Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India. Indian J Crit Care Med 2023;27(8):552-562.

Impact of Reduced Enoxaparin Prophylactic Dosing on Bleeding and Thrombotic Risk for Low Body Weight Post-Operative Colorectal Surgery Patients.

Introduction: Colorectal surgery (CORS) patients are at the highest risk of any general surgery population for the development of post-operative venous thromboembolism (VTE) and are also at an increased risk for post-operative bleeding, especially with procedures related to early cancer stages. Low molecular weight heparin (LMWH) is recommended for VTE prophylaxis in this surgical population. Current guidelines and primary literature along with institutional protocols support dosage adjustments for obesity and impaired renal function, but literature providing optimal VTE prophylactic LMWH dosing is extremely limited for underweight, surgical patients. Objectives: The aim of this study was to evaluate both bleeding and VTE rates for hospitalized underweight colorectal surgery patients receiving post-operative VTE prophylaxis with standard enoxaparin 40 mg subcutaneously (SQ) every 24 hours versus reduced dose enoxaparin 30 mg SQ every 24 hours. Methods: This trial was a multicenter, retrospective chart review with data collected on post-operative CORS patients over a 10-year period. Patients were included if aged 18 years and older, weighed less than 50 kg, and received at least 1 dose of enoxaparin 40 mg or 30 mg post-operatively. The primary endpoint was a descriptive comparison of post-operative bleeding with use of standard enoxaparin 40 mg SQ every 24 hours compared to reduced dose enoxaparin 30 mg SQ every 24 hours for post-operative VTE prophylaxis. The secondary endpoint was the descriptive comparison of post-operative thrombotic event rates in the same population. Results: The total population investigated included 146 patients. One hundred twenty-nine (88.4%) received standard enoxaparin and 17 (11.6%) received reduced enoxaparin. Overall, 9 bleeding events (7.0%) and 2 major VTE events (1.6%) occurred, all within the standard enoxaparin group. Conclusion: Standard dose enoxaparin for post-operative VTE prophylaxis demonstrated increased bleeding and thrombotic events requiring medical and surgical intervention in comparison to reduced dose enoxaparin for low body weight CORS patients. The results of this study are hypothesis generating and continued research involving more robust systematic reviews are needed to evaluate both safety and efficacy of reduced VTE prophylaxis with LMWH in the underweight, surgical patient population.

P454 No increased postoperative risk of venous thromboembolism nor infectious complications after JAK inhibitor exposure in patients with ulcerative colitis undergoing colectomy

Abstract Background Total colectomy for ulcerative colitis (UC) is associated with postoperative morbidity, including venous thromboembolism (VTE), in patients who already have a 2 to 4-fold risk for thromboembolic events. In light of recent concerns on increased major adverse events associated with JAK inhibitor exposure, we aimed to evaluate the postoperative VTE risk as well as other (non)infectious complications in UC patients undergoing colectomy after JAK inhibitor use. Methods This retrospective cohort study included all UC patients who underwent colectomy between 2013 and 2021 in our tertiary IBD center, and documented the 180-day postoperative non-infectious and infectious risks (table 1). Clinically relevant information included patient demographics, comorbidities, family history of IBD, personal history of VTE, intake of oral anticonception, smoking behaviour, disease characteristics including indication for colectomy, preoperative serum laboratory values, perioperative drug exposure (table 2) and surgical characteristics including low-molecular weight heparin (LMWH) prophylaxis (table 3). Results One-hundred seventy-nine UC patients (43.6% women, median [IQR] age 42.0 [28.5 – 56.2] years) underwent colectomy due to refractory disease (n=154) or suspected dysplasia or carcinoma (n=25). Forty-nine patients (27.4%) were operated urgently. In the twelve weeks prior to surgery, 55 (30.7%) patients had received anti-TNF agents, 40 (22.3%) anti-adhesion therapy, 16 (8.9%) anti-IL12/23, 2 (1.1%) investigational agents and 36 (20.1%) JAK inhibitors. Preoperatively, 27 patients (15.1%) were administered a moderate to high dose of systemic corticosteroids. All patients received antithrombotic prophylactic LMWH postoperatively, except for two patients who developed a gastrointestinal bleeding. During the 180-day postoperative period, a total of 3 patients (1.7%; mean age 51 years, 1 female) developed an intra-abdominal thrombosis, found by coincidence on CT scan. In all patients risk factors were identified, e.g. inflammatory state, cancer, high dose of corticosteroids. No VTE was seen in the patients who underwent colectomy while on JAK inhibitor. Only two out of 36 JAK inhibitor treated patients (5.6%) developed an infectious complication, while the overall risk of developing an infectious complication was 19.5%. Conclusion The overall risk for UC patients to develop VTE after colectomy is low with adequate antithrombotic prophylactic therapy. We did not observe any VTE in patients who were exposed to JAK inhibitors prior to surgery, nor did we see an increased risk on short-term infectious complications in this patient group. All patients who developed VTE despite LMWH had additional risk factors.

Preoperative Venous Thromboembolism Screening and Postoperative Selective Anticoagulant Therapy Effectively Prevents Postoperative Symptomatic Venous Thromboembolism in Gynecological Malignancies: A 15-Year, Single-Center Study.

The aim of this study was to determine which type of prophylaxis was effective for postoperative symptomatic venous thromboembolism (VTE) in patients with gynecological malignancies. A total of 1756 consecutive patients undergoing laparotomy as first-line treatment were included. In Period 1 (2004-2009), low-molecular weight heparin (LMWH) was not available for postoperative VTE prophylaxis, but available in after Period 2 (2009-2013). In Period 3 (2013-2020), patients with pretreatment VTE could switch from LMWH to direct oral anticoagulant (DOAC) as of 2015. Preoperative VTE was screened by measuring D-dimer, followed by venous ultrasound imaging, and computed tomography and/or perfusion lung scintigraphy. Postoperative symptomatic VTE occurred with an incidence of 2.8% by the measures without prophylactic LMWH administration in Period 1. The incidence of postoperative symptomatic VTE was 0.6% in Period 2 and 0.3% in Period 3, being significantly reduced compared with Period 1 (P < .01 and < .0001). The incidences were not significantly different between Periods 2 and 3, but no patient switching to DOAC in Period 3 (n = 79) developed symptomatic VTE. Our preoperative VTE screening and postoperative selective LMWH administration were significantly preventive against postoperative symptomatic VTE.

Anesthetic Management in Parturients With Fontan Physiology

Anesthetic Management in Parturients With Fontan Physiology

Low-molecular-weight heparin compared with unfractionated heparin in critically ill COVID-19 patients

BackgroundThrombosis in COVID-19 worsens mortality. In our study, we sought to investigate how the dose and type of anticoagulation (AC) can influence patient outcomes. MethodsThis is a single-center retrospective analysis of critically ill intubated patients with COVID-19, comparing low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) at therapeutic and prophylactic doses. Of 218 patients, 135 received LMWH (70 prophylactic, 65 therapeutic) and 83 UFH (11 prophylactic, 72 therapeutic). The primary outcome was mortality. Secondary outcomes were thromboembolic complications confirmed on imaging and major bleeding complications. Cox proportional-hazards regression models were used to determine whether the type and dose of AC were independent predictors of survival. We performed Kaplan-Meier survival analysis to compare the cumulative survivals. ResultsOverall, therapeutic AC, with either LMWH (65% vs 79%, P = .09) or UFH (32% vs 46%, P = .73), conveyed no survival benefit over prophylactic AC. UFH was associated with a higher mortality rate than LMWH (66% vs 28%, P = .001), which was also evident in the multivariable analysis (LMWH vs UFH mortality, hazard ratio: 0.47, P = .001) and in the Kaplan-Meier survival analysis. Thrombotic and bleeding complications did not depend on the AC type (prophylactic LMWH vs UFH: thrombosis P = .49, bleeding P = .075; therapeutic LMWH vs UFH: thrombosis P = .5, bleeding P = .17). When comparing prophylactic with therapeutic AC, the rate of both thrombotic and bleeding complications was higher with the use of LMWH compared with UFH. In addition, transfusion requirements were significantly higher with both therapeutic LMWH and UFH. ConclusionsAmong intubated critically ill COVID-19 intensive care unit patients, therapeutic AC, with either LMWH or UFH, conveyed no survival benefit over prophylactic AC. AC with LMWH was associated with higher cumulative survival compared with AC with UFH.

Delayed Cranial Decompression Rates After Initiation of Unfractionated Heparin versus Low-Molecular-Weight Heparin in Traumatic Brain Injury

Both unfractionated heparin (UH) and low-molecular-weight heparin (LMWH) are routinely used prophylactically after traumatic brain injury (TBI) to prevent deep vein thrombosis (DVT). Their comparative risk for development or worsening of intracranial hemorrhage necessitating cranial decompression is unclear. Furthermore, the absence of a specific antidote for LMWH may lead to UH being used more often for high-risk patients. This study aims to compare the incidence of delayed cranial decompression occurring after initiation of prophylactic UH versus LMWH using the National Trauma Data Bank. Cranial decompression procedures included craniotomy and craniectomy. Multiple imputation was used for missing data. Propensity score matching was used to account for selection bias between UH and LMWH. The 1:1 matched groups were compared using logistic regression for the primary outcome of postprophylaxis cranial decompression. A total of 218,594 patients with TBI were included, with 61,998 (28.3%) receiving UH and 156,596 (71.7%) receiving LMWH as DVT prophylaxis. The UH group had higher patient age, body mass index, comorbidity rates, Injury Severity Score, and worse motor Glasgow Coma Scale score. After the UH and LMWH groups were matched for these factors, logistic regression showed lower rates of postprophylaxis cranial decompression for the LMWH group (odds ratio, 0.13; 95% confidence interval, 0.11-0.16; P < 0.001). Despite the absence of a specific antidote, LMWH was associated with lower rates of need for post-DVT-prophylaxis in craniotomy/craniectomy. This finding questions the notion of UH being safer for patients with TBI because it can be readily reversed. Randomized studies are needed to elucidate causality.

Electronic prescribing systems as tools to improve patient care: a learning health systems approach to increase guideline concordant prescribing for venous thromboembolism prevention

BackgroundVenous thromboembolism (VTE) causes significant mortality and morbidity in hospitalised patients. Risk factors for VTE are well known and there are validated risk assessment tools to support the use of prophylactic therapies. In England, reporting the percentage of patients with a completed VTE risk assessment is mandated, but this does not include whether that risk assessment resulted in appropriate prescribing. Full guideline compliance, defined as an assessment which led to an appropriate action—here prescribing prophylactic low molecular weight heparin where indicated, is rarely reported. Education, audit and feedback enhance guideline compliance but electronic prescribing systems (EPS) can mandate guideline-compliant actions. We hypothesised that a systems-based EPS intervention (prescribing rules which mandate approval or rejection of a proposed prescription of prophylactic low molecular weight heparin based on the mandated VTE assessment) would increase full VTE guideline compliance more than interventions which focused on targeting individual prescribers.MethodsAll admitted patients within University Hospitals Birmingham NHS Foundation Trust were included for analysis between 2011 and 2020. The proportion of patients who received a fully compliant risk assessment and action was assessed over time. Interventions included teaching sessions and face-to-face feedback based on measured performance (an approach targeting individual prescribers) and mandatory risk assessment and prescribing rules into an EPS (a systems approach).ResultsData from all 235,005 admissions and all 5503 prescribers were included in the analysis. Risk assessments were completed in > 90–95% of all patients at all times, but full guideline compliance was lower (70% at the start of this study). Face-to-face feedback improved full VTE guideline compliance from 70 to 77% (p ≤ 0.001). Changes to the EPS to mandate assessment with prescribing rules increased full VTE compliance to 95% (p ≤ 0.001). Further amendments to the EPS system to reduce erroneous VTE assessments slightly reduced full compliance to 92% (p < 0.001), but this was then maintained including during changes to the low molecular weight heparin used for VTE prophylaxis.DiscussionAn EPS-systems approach was more effective in improving sustained guideline-compliant VTE prevention over time. Non-compliance remained at 8–5% despite this mandated system. Further research is needed to assess the potential reasons for this.

Prophylactic anticoagulation with low molecular weight heparin in COVID-19: cohort studies in Denmark and Sweden

ObjectivesTo evaluate safety and effectiveness of prophylactic anticoagulation with low molecular weight heparin (LMWH) in individuals hospitalised for COVID-19. MethodsUsing healthcare records from the Capital Region of Denmark (March 2020-February 2021) and Karolinska University Hospital in Sweden (February 2020-September 2021), we conducted an observational cohort study comparing clinical outcomes 30 days after admission among individuals hospitalised for COVID-19 starting prophylactic LMWH during the first 48 hours of hospitalisation with outcomes among those not receiving prophylactic anticoagulation. We used inverse probability weighting to adjust for confounders and bias due to missing information. Risk ratios, risk differences and robust 95% confidence intervals (CI) were estimated using binomial regression. Country-specific risk ratios were pooled using random-effects meta-analysis. ResultsWe included 1692 and 1868 individuals in the Danish and Swedish cohorts. Of these, 771 (46%) and 1167 (62%) received prophylactic LMWH up to 48 hours after admission. The combined mortality in Denmark and Sweden was 12% (N = 432) and the pooled risk ratio was 0.91 (CI 0.60-1.38) comparing individuals who received LMWH to those who did not. The relative risk of ICU admission was 1.12 (0.76-1.66), while we observed no increased risk of bleeding 0.63 (0.13-2.94). The relative risk of venous thromboembolism was 0.80 (0.43-1.47). ConclusionWe found no benefit on mortality with prophylactic LMWH and no increased risk of bleeding among COVID-19 patients receiving prophylactic LMWH.

118 Delayed Cranial Decompression Rates After Initiation of Unfractionated Heparin Versus Low-Molecular-Weight Heparin in Traumatic Brain Injury

INTRODUCTION: Both unfractionated heparin (UH) and low-molecular weight heparin (LMWH) are routinely used prophylactically after traumatic brain injury (TBI) to prevent deep vein thrombosis. Their comparative risk for intracranial hemorrhage (ICH) development or worsening necessitating cranial decompression after prophylaxis initiation is unclear. Furthermore, the absence of a specific antidote for LMWH may lead to UH being used more often for high-risk patients. METHODS: We compared the incidence of delayed cranial decompression occurring after initiation of prophylactic UH vs. LMWH using the National Trauma Data Bank. Cranial decompression procedures included craniotomy, craniectomy, and external ventricular drain placement. Multiple imputation was utilized for missing data. To account for selection bias between UH and LMWH, we conducted propensity score matching using factors that were significantly different between the two groups. The matched UH and LMWH groups were then compared using logistic regression for the primary outcome of post-prophylaxis cranial decompression. RESULTS: A total of 218,594 TBI patients were included, with 61,998 (28.3%) receiving UH and 156,596 (71.7%) receiving LMWH as DVT prophylaxis. The UH group had significantly higher patient age, BMI, comorbidity rates, injury severity score, and worse motor Glasgow coma scale. After matching the UH and LMWH groups for these factors, logistic regression demonstrated lower rates of post-prophylaxis cranial decompression for the LMWH group (OR 0.13, 95% CI 0.11-0.16, P &lt; 0.001). CONCLUSION: Despite the absence of a specific antidote, LMWH was associated with substantially lower rates of post-DVT-prophylaxis cranial decompression. This indicates that UH may not be the safer alternative in TBI patients at high risk for intracranial hemorrhagic complications.

Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis.

Trauma patients have simultaneously high venous thromboembolism (VTE) and bleeding risk. Optimal chemoprophylaxis regimens remain unclear. This study aims to answer three questions for trauma patients. Is there any association between anti-Xa and VTE? Does dose adjustment improve prophylactic anti-Xa rates? Does dose adjustment improve anti-Xa adequacy and VTE compared with standard dosing? Systematic search of MEDLINE, Embase, Scopus, and Web of Science occurred in May 2021. Two author reviews included trauma studies that evaluated low molecular weight heparin chemoprophylaxis, reported anti-Xa level, and evaluated more than one outcome. Data were dually extracted and estimated effects were calculated using RevMan 5.4 applying the Mantel-Haenszel method. Analysis 1 compared patients with peak anti-Xa of 0.2 IU/mL or greater or trough 0.1 IU/mL or greater to those with lower anti-Xa using VTE as the primary outcome. Analysis 2 reported the effect of dose adjustment on anti-Xa. Analysis 3 compared standard dosing to dose adjustment with the primary outcome being anti-Xa adequacy; secondary outcomes were VTE, pulmonary embolism, and bleeding complications. There were 3,401 studies evaluated with 24 being included (19 retrospective studies, 5 prospective studies). In analysis 1, achieving adequate anti-Xa was associated with reduced odds of VTE (4.0% to 3.1%; odds ratio [OR], 0.52; p = 0.03). Analysis 2 demonstrated that 768 (75.3%) patients achieved prophylactic anti-Xa with adjustment protocols. Analysis 3 suggested that dose-adjusted chemoprophylaxis achieves prophylactic anti-Xa more frequently (OR, 4.05; p = 0.007) but without VTE (OR, 0.72; p = 0.15) or pulmonary embolism (OR, 0.48; p = 0.10) differences. In subgroup analysis, anti-Xa dose adjustment also suggested no VTE reduction (OR, 0.68; p = 0.08). Patients with higher anti-Xa levels are less likely to experience VTE, and anti-Xa guided chemoprophylaxis increases anti-Xa adequacy. However, dose adjustment, including anti-Xa guided dosing, may not reduce VTE. Systematic Review Meta-Analysis, Level IV.

Pathogenesis, Diagnosis and Management of Obstetric Antiphospholipid Syndrome: A Comprehensive Review.

Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity associated with persistent antiphospholipid antibody positivity. Cases fulfilling the Sydney criteria for obstetric morbidity with no previous thrombosis are known as obstetric antiphospholipid syndrome (OAPS). OAPS is the most identified cause of recurrent pregnancy loss and late-pregnancy morbidity related to placental injury. Cases with incomplete clinical or laboratory data are classified as obstetric morbidity APS (OMAPS) and non-criteria OAPS (NC-OAPS), respectively. Inflammatory and thrombotic mechanisms are involved in the pathophysiology of OAPS. Trophoblasts, endothelium, platelets and innate immune cells are key cellular players. Complement activation plays a crucial pathogenic role. Secondary placental thrombosis appears by clot formation in response to tissue factor activation. New risk assessment tools could improve the prediction of obstetric complication recurrences or thromboses. The standard-of-care treatment consists of low-dose aspirin and prophylactic low molecular weight heparin. In refractory cases, the addition of hydroxychloroquine, low-dose prednisone or IVIG improve pregnancy outcomes. Statins and eculizumab are currently being tested for treating selected OAPS women. Finally, we revisited recent insights and concerns about the pathophysiology, diagnosis and management of OAPS.

A Prospective Study Assessing Wound Complications in a Series of Foot and Ankle Patients Treated With Enoxaparin: A Baseline for Future Studies.

Background and objectiveLow-molecular-weight heparin (LMWH) prophylaxis has now become the gold-standard practice in patients requiring lower limb immobilization. We had noticed an increase in the incidence of wound-healing problems at our center, and the severity of the problems was found to be worse in patients undergoing foot and ankle surgery since we had adopted this practice. In this study, we aimed to describe the incidence and severity of wound-healing problems in this group of patients.MethodsThis was a prospective study and we collected data on the frequency and severity of wound problems occurring in patients undergoing a variety of foot and ankle operations. All patients underwent a standard agreed-on method of wound closure and dressings. Wounds were reviewed after two weeks and wound characteristics were noted using a rigid proforma. The primary outcome measure was to determine the incidence of delayed wound healing (DWH) and wound infections requiring antibiotics. Secondary outcomes were the characteristics of each delayed-healing wound.ResultsA total of 158 patients met the inclusion criteria of the study. One patient was not given postoperative LMWH and was excluded from the final analysis. Seven patients (4.5%) were noted to have DWH and four patients (2.6%) had a wound infection at the two-week postoperative follow-up. None of the patients required a second operation. Among patients with wound-healing problems, wound contour irregularities were noted in 51% and margin separation was noted in 65%.ConclusionThe overall incidence of wound-healing problems such as DWH and wound infections was low in patients receiving prophylactic LMWH for foot and ankle surgery. Where postoperative wound problems did occur, these were associated with poor wound characteristics such as margin separation or contour irregularity. Further studies should be conducted to ascertain if the use of LMWH leads to problems with wound appearance.

Prophylaxis for venous thromboembolism in liver disease: a narrative literature review

Background: Patients with liver disease have traditionally been regarded as auto-anticoagulated against developing blood clots due to haemorrhage being regarded as the most significant haemostatic complication. More recently, there has been increasing recognition that hypercoagulability is a prominent aspect of cirrhosis, with an increasing number of patients developing thromboembolisms. When prescribing prophylactic low molecular weight heparin for prevention, clinicians are often concerned about the risk of bleeding, including gastrointestinal bleeding, specifically in those with decompensated liver disease and cirrhosis, due to the altered coagulopathy associated with these patients. Aim: The aim of this review was to assess if the use of prophylaxis in patients with liver disease is effective in the prevention of venous thromboembolism (VTE) and whether its use is related to an increase in bleeding episodes. Methods: A review of the literature was conducted to identify the incidence of VTE and bleeding in liver patients when given prophylactic VTE treatment. Results: The majority of evidence was inconclusive; however, the main emerging theme was that administering prophylaxis to patients with decompensated liver disease results in an increased risk of bleeding, while having little effect on reducing the risk of VTE development. Conclusion: The bleeding risk associated with VTE prophylaxis treatment and liver disease remains uncertain. Thus the ideal methods of medical prophylactic VTE prevention and monitoring in this patient population have not yet been determined. It is suggested that additional consideration should be given to serum albumin, platelet count and international normalised ratio, as well as renal function, in conjunction with risk assessment tools, when deciding whether to prescribe VTE prophylaxis or not.

Is The Risk of Thromboembolic Disease and Bleeding Adequately Evaluated in Patients with Glioblastoma? A Review of The Topic

Introduction: Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor, with an aggressive course and a short life expectancy despite standard treatment (chemotherapy and radiotherapy). The possibility of the development of thrombotic events (VTE) with this type of cancer is frequent. Objective: To determine the risk of presenting VTE and haemorrhagic events in patients affected by GBM. Methods: Observational retrospective study of patients with GBM diagnosis at the General University Hospital of Ciudad Real between 2012 and 2015. The demographic characteristics of patients were studied, predictive models were compared, and a survival analysis was performed. Results: 77 patients were studied, 42 (55.3%) / 34 (44.7%), men and women respectively, with an average age of 66.42 years. 13 (16.9%) presented VTE; of which 10 (61.54%) in the form of deep venous thrombosis (DVT), 3 (23.08%) pulmonary embolism (PE) and 2 (15.38%) mixed events. The quality of life according to the performance status ECOG scale at the moment of diagnosis was 1 in 42 (15.38%) patients, and at the time of VTE, 5 (41.7%) had a value of 2, and 4 (33.3.3 %) registered 3. In the group that developed VTE according to the predictive model of risk for thrombosis in Khorana 5 (38.5%) had low risk and 8 (61.5%) intermediate; on the ASCO 2013 modified scale 5 (38.5%) had an Intermediate risk and 8 (61.5%) high. With a median, 1 year follow-up, 64 (84.2%) patients died, with an average time after the diagnosis of 279.09 days (216.6-341.6) (SE 31,8). 2 (2.6%) of the patients presented a greater haemorrhagic event and 7 (7.9%) cerebral haemorrhage, of which 4 (44.4%) had prophylactic Low molecular weight heparins (LMWHs). In the survival analysis of Kaplan Meyer, patients who received prophylactic treatment with LMWHs had a higher survival rate with an average of 298.5 days compared to 239.3 of those who did not (p&gt; 0.05). There were no significant variables in the multivariate analysis for thrombotic or haemorrhagic events. Conclusion and Discussion: The demographic and clinical characteristics of our patients were similar to those reported in other international publications. The predictive scale of Khorana was not validated in our study, in contrast, the modified ASCO 2013 scale was closer to our results. The creation of a precise predictive model would help to delineate the benefit of prophylactic anticoagulation in high-risk patients. Long-term prophylaxis with LMWHs has demonstrated a reduction of thrombotic events without significantly increasing the fatal haemorrhagic episodes, also demonstrating greater long-term survival, independent of thrombotic events. Randomized prospective studies are needed to demonstrate its benefits.

Prophylactic Low-Molecular-Weight Heparin Versus Unfractionated Heparin in Spine Surgery (PLUSS): A Pilot Matched Cohort Study.

Despite a proven superior efficacy of prophylactic low-molecular-weight heparin (LMWH) over unfractionated heparin (UFH) in the majority of surgical specialties, chemoprophylactic techniques after spine surgery have not been established because of the fear of epidural hematomas with LMWH. To determine the efficacy of LMWH vs UFH in the prevention of venous thromboembolism (VTE) events, balanced against the risk of epidural hematoma. This is the first matched cohort design that directly compares prophylactic LMWH to UFH after spine surgery for degenerative/deformity pathologies at a tertiary academic center. Prospectively collected patients receiving prophylactic LMWH and a historical cohort of patients receiving prophylactic UFH (prior to 2017) were matched in 1:1 ratio based on age ±5 yr, American Society of Anesthesiologists classification, location in the spinal column, and type of surgery. Of 562 patients, VTE events equaled 1.4% (n=8): 1.4% (n=4) with LMWH was exactly equal to 1.4% (n=4) with UFH. Epidural hematomas reached 0.8% (n=5): 1.4% (n=4) with UFH vs 0.3% (n=1) with the LMWH (P=.178). Utilizing adjusted odds ratio (ORadj), the type of chemoprophylaxis after spine surgery failed to predict VTE events. Similarly, the chemoprophylactic technique failed to predict epidural hematoma in the multivariable regression analysis, although UFH trended toward a higher complication rate (ORadj=3.15 [0.48-20.35], P=.227). Chemoprophylactic patterns failed to predict VTE. Although no differences in epidural hematoma rates were detected, our analysis does highlight a trend toward a safer profile with LMWH vs UFH. LMWH may be a safe alternative to UFH in spine surgery.

Progression of Intracranial Hemorrhage After Chemical Prophylaxis Using Low-Molecular-Weight Heparin in Patients With Traumatic Brain Injury.

Chemical prophylaxis using low-molecular-weight heparin (LMWH) is considered a standard of care for venous thromboembolism in trauma patients. Our center performs a head computed tomography (CT) scan 24 hours after initiation with prophylactic LMWH in the setting of a known traumatic brain injury (TBI). The purpose was to determine the overall incidence of ICH progression after chemoprophylaxis in patients with a TBI. This retrospective study was performed at a Level I trauma center, from 1/1/2014 to 12/31/2017. Study patients were drawn from the institution's trauma registry based on Abbreviated Injury Score codes. 778 patients met all inclusion criteria after initial chart review. The proportion of patients with an observed radiographic progression of intracranial hemorrhage after LMWH was 5.8%. 3.1% of patients had a change in clinical management. Observed radiographic progression after LMWH prophylaxis and the presence of SDH on initial CT, the bilateral absence of pupillary response in the emergency department, and a diagnosis of dementia were found to have statistically significant correlation with bleed progression after LMWH was initiated. Over a 4-year period, the use of CT to evaluate for radiographic progression of traumatic intracranial hemorrhage 24 hours after receiving LMWH resulted in a change in clinical management for 3.1% of patients. The odds of intracranial hemorrhage progression were approximately 6.5× greater in patients with subdural hemorrhage on initial CT, 3.1× greater in patients with lack of bilateral pupillary response in ED, and 4.2× greater in patients who had been diagnosed with dementia.