Hypercoagulability Complications Research Articles

Prevalence of Asymptomatic COVID-19 Infection in Hemodialysis Patients and the Risk of Hypercoagulability: Should we Consider Routine Screening?

Coronavirus disease 2019 (COVID-19) has become a pandemic in late 2019. Its clinical presentation varies from asymptomatic infection to severe respiratory failure. Infection control strategies to minimize the risk of transmission of COVID-19 in end-stage renal disease (ESRD) patients receiving in-center hemodialysis (HD) have been implemented. Development of humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in adult patients with ESRD receiving HD has not been sufficiently reported. A total of 179 asymptomatic HD patients undergoing regular HD were screened for COVID-19 infection. Infection with SARS-CoV-2 was confirmed through a real-time reverse transcription polymerase chain reaction assay of nasopharyngeal swab specimens. They were classified into positive and negative groups according to the results of PCR. Of the 179 asymptomatic patients, we found that 23 patients (12.8%) were positive for COVID-19. Their mean age was 45.61 ± 13.38 years. There was a significant difference between both groups regarding C-reactive protein, lymphocytes, and platelet counts (P < 0.001). Also, TAT (thrombin-antithrombin complex) and D-dimer levels were significantly increased among the positive group (11.47 ± 1.51 vs. 7.53 ± 1.64 mcq/L, P < 0.001; 1171.52 ± 267.6 vs. 542.76 ± 107.06 ng/mL, P < 0.001, respectively). Asymptomatic SARS-CoV-2 infection is detected in HD patients. They carry the risk of hypercoagulability complications. We need more strict infection control measures and proactive diagnosis to limit the spread of the infection and lethal thromboembolic complications.

Heparin for patients with coronavirus disease 2019 and hypercoagulation complications: A cohort study

BackgroundThrombotic complications of coronavirus disease 2019 (COVID-19) are a worrisome aspect of the disease due to their high incidence in critically ill patients and their poor clinical outcomes. The aim of this study was to compare the effectiveness of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) (fondaparinux) in hospitalized COVID-19 patients with hypercoagulable complications. Material and methodsThe study design used a retrospective cohort approach incorporating pre- and post-tests via secondary data extracted from the medical records of inpatients with confirmed COVID-19. ResultsAmong the 98 individuals studied (52% women; 30.6% at >60 years of age), 35 patients received UFH, while the remaining 63 patients received LMWH (fondaparinux). The greatest decrease in the D-dimer value (0.01 ± 0.5 g fibrinogen equivalent units/mL) was observed in 12 (34.3%) and 15 (23.8%) patients in the UFH and LMWH (fondaparinux) groups, respectively. Most inpatients with confirmed COVID-19 were aged 50–59 years and were women. ConclusionThere was a tendency toward increased D-dimer, normal prothrombin time, normal activated partial thromboplastin clotting time, and increased fibrinogen values in each COVID-19 patient. The results demonstrated a significant relationship between the D-dimer and prothrombin time parameter in confirmed COVID-19 inpatients.

Transplanting Thoracic COVID-19 Positive Donors: Overcoming the Pandemic

PurposeThe COVID19 pandemic has exacerbated the thoracic organ shortage. Safe donation from COVID19 infected donors would increase the donor pool.MethodsWe present our institutional protocol and early results for thoracic organ transplantation using COVID19 positive donors.EndpointsTo date, we performed 10 thoracic organ transplants in 9 recipients using organs from COVID19 positive donors (9 hearts;1 pair of lungs). Patient and graft survival to date is 100%, 91%.Hearts were procured from donors testing positive for COVID19 on upper and/or lower respiratory tract specimens, provided severe COVID pneumonia or myocarditis was not the cause of death, and hypercoagulable complications were absent. Lungs were procured only if donors were first positive >20 days prior and were PCR-negative on bronchoalveolar lavage. Cycle threshold, duration of infectivity and urgency of recipient need were considered in addition to routine evaluations.8/10 donors were first detected positive during terminal illness, yet no heart recipients acquired COVID19 infection through transplant and no unexpected rejection occurred. 1 heart-liver recipient required a redo heart transplant due to massive hemorrhage followed by hypercoagulability and coronary thrombus. An RV biopsy from the donor heart demonstrated ischemic changes and SARS-CoV-2 immunohistochemical findings suspicious for myocyte infiltration. Urgent re-transplantation was successfully completed utilizing a heart from another COVID19+ donor with no recurrence of hypercoagulability. One patient received lungs from a donor with mild COVID19, first detected 38 days earlier, yet still COVID19 positive on nasopharyngeal swab but not on BAL. No procurement or care team members became infected with covid as a result of this protocol.While limited, our experience to date supports that use of hearts from COVID19 positive donors is safe and effective. Lung transplantation from COVID19 positive donors is unresolved but may be cautiously pursued under the restricted circumstances.

Thrombotic and Hypercoagulability Complications of COVID-19: An Update

The current COVID-19 pandemic emerged in December 2019, in China, affecting millions of people worldwide. COVID-19 is mainly a disease of the respiratory system, yet systematic complications have also been reported among SARS-CoV-2 infected patients. Thrombotic complications are one of the severe clinical outcomes of COVID-19, especially among critically ill patients, and are associated with poor prognosis. To date, many studies have concluded that COVID-19 increases the incidence of thrombotic events and coagulopathies; however, the exact mechanism behind such a disease outcome is not well known. Various pathophysiological mechanisms for thrombotic events in COVID-19 have been proposed, these include virus-induced endothelial cell damage, inflammation, and excess production of pro-inflammatory cytokines. As a result, most critically diseased COVID-19 patients are managed with prophylactic anticoagulant, yet some still develop thrombotic episodes. Therefore, better understanding of the mechanisms behind the thrombotic complications is needed to develop treatments that specifically target such pathways, which may aid in better disease management and improve the prognosis.

The Effect of Systemic Tranexamic Acid on Hypercoagulable Complications and Perioperative Outcomes Following Three-Column Osteotomy for Adult Spinal Deformity.

Study Design:Retrospective cohort study.Objective:Thoracolumbar 3-column osteotomy (3CO) is a powerful technique for correction of rigid adult spinal deformity (ASD). However, it can be associated with high-volume blood loss. This study seeks to investigate the efficacy and safety of tranexamic acid (TXA) in 3CO ASD patients.Methods:ASD patients who underwent 3CO from 2006 to 2019 were retrospectively reviewed. Outcomes were compared between TXA and non-TXA patients, and TXA doses.Results:A total of 365 ASD patients were included: 181 TXA and 184 non-TXA. The mean age was 64.6 years and 60.5% were female. Operative time was shorter in the TXA group (295.6 vs 320.2 minutes, P < .001). However, TXA was not associated with shorter operative time (β = −6.5 minutes, 95% CI −29.0 to 15.9, P = .567) after accounting for surgeon experience. There was no difference in blood loss (2020.2 vs 1914.1 mL, P = .437) between groups. Overall complications (37.0% vs 33.2%, P = .439), including hypercoagulable (2.2% vs 3.8%, P = .373) and cardiac (13.3% vs 7.1%, P = .050) complications were similar between groups. TXA was not independently associated with blood loss or TXA-related complications. Both groups had comparable intensive care unit (2.5 vs 2.0 days, P = .060) and hospital (8.9 vs 8.2 days, P = .190) stays. There were no differences in outcomes between TXA dosing subgroups.Conclusions:Systemic TXA use during 3CO for ASD surgery was not associated with decreased blood loss. TXA patients had shorter operative times, but this was driven mainly by surgeon experience on multivariate analysis. Routine use of TXA is safe and does not increase the incidence of hypercoagulable complications even at high doses.

Unique Patterns of Cardiovascular Involvement in Coronavirus Disease-2019

Coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains a global pandemic. Although COVID-19 was initially thought to be a disease largely characterized by respiratory disease and a fever, subsequent data have highlighted this clinical scope was too narrow. Indeed, the majority of individuals infected with SARS-CoV-2 may be asymptomatic, although others present with a variety of symptoms including cardiac, neurologic, and hypercoagulable complications.

Thrombotic Cutaneous Gangrene: A Rare Dermatologic and Hematologic Extraintestinal Manifestation of Ulcerative Colitis

Ulcerative colitis (UC) is associated with many extraintestinal manifestations, which can include dermatologic and hematologic involvement. Thrombotic cutaneous gangrene (TCG) is a rare dermatologic and hematologic complication with potentially poor prognosis, often needing colectomy in addition to anti-coagulation for complete resolution. A 33-year-old healthy female presented with chronic bloody diarrhea and was diagnosed with left sided UC. She was initiated on steroids and discharged on a prednisone taper. Three days after discharge, she presented with fever and progressive and extensive racemose and retiform purpura on her trunk and extremities. She continued to have bloody stool despite adherence to prednisone. Areas of purpura evolved to tense bullae which erupted. She had an elevated D-dimer, prolonged PT, and reduced anti-thrombin III activity. Complete antiphospholipid syndrome panel was negative. A skin punch biopsy showed thrombotic vasculopathy involving small dermal vasculature without vasculitis. No other end-organ complications of hypercoagulability were identified. MRE showed inflammatory changes limited to the descending colon, sigmoid colon, and rectum, with no involvement of the small bowel. Anti-thrombin III levels were replenished, high dose heparin drip was started, and her hypercoagulable state resolved. The patient's UC was refractory to steroids; she was subsequently started on Infliximab, which controlled her luminal symptoms. She was discharged on Lovenox, which significantly improved her skin manifestations. Our case underlines the importance of appreciating a hypercoagulable state in UC and suspecting TCG in UC cases presenting with rapidly progressing purpura. Immediate hypercoagulability work up, skin biopsy, and anticoagulation should be initiated to prevent further complications. Furthermore, we demonstrate that trial of biologic immunosuppressive therapy may prevent need for colectomy to treat TCG.2098_A Figure 1. Retiform purpura on shoulder and back2098_B Figure 2. Areas of purpura evolved to become tense bullae which eventually erupted.2098_C Figure 3. Mayo 3 UC

Activated platelets and leukocyte activations in young patients with β-thalassemia/HbE following bone marrow transplantation

Bone marrow transplantation (BMT) is the only curable option for thalassemia major, β-thalassemia/HbE. However, some patients still have the risk of hypercoagulable complications. We used a whole blood flow cytometric analysis to measure the circulating microparticle (MP) levels, activated platelets, and leukocyte-platelet aggregates in 59 young β-thalassemia/HbE patients compared with 20- and 28-matched healthy and patients receiving regular blood transfusion (RT), respectively. Results from the studies showed that blood samples from BMT group contained a significantly higher numbers of circulating MPs originated from platelets (ann-V+CD41a+), leukocyte (ann-V+CD45+) and endothelial cells (ann-V+CD146+) when compared to samples from healthy subjects and RT patients. In contrast, the percentages of activated/procoagulant platelets (CD62P and CD142 expressing platelets) were decreased in BMT group. In addition, monocytes forming microaggregates were the major population among other leukocyte-platelet complexes. Different patterns of CD11b, CD62P and CD142 expression on platelet-leukocyte microaggregate surface were also found. These data suggest that circulating MPs together with leukocyte-platelet aggregates may be responsible, in part, in pathogenesis of hypercoagulable state in β-thalassemia/HbE patients who undergone BMT.

Viscoelastic Testing in Liver Disease

Long thought to be hypocoagulable, new evidence suggests cirrhosis patients have “rebalanced” coagulation in the setting of decreased synthesis of both pro- and anti-coagulant factors. Traditional testing like PT/INR reflects only the decreased synthesis of pro-coagulant factors and thus does not correspond to bleeding or clotting risk in this population. In this review, we discuss the use of viscoelastic testing (VET), an assay of global hemostasis in cirrhosis patients. We describe the technique and interpretation of commercially available VET and assess the application of VET in both transplant and non-transplant cirrhosis populations. VET largely correlates well with traditional testing including platelet count and fibrinogen level, however, is potentially less accurate in patients with low fibrinogen levels. VET may be useful in identifying patients at higher risk of hypercoagulable complications post-transplant and reflects changes in hemostasis in decompensated patients. While VET has been associated with decreased transfusion support in multiple studies, the lack of bleeding in patients who avoided prophylactic transfusion suggests a “rescue” rather than prophylactic approach to transfusion may be ideal and further studies with a “rescue” arm are needed. Additional prospective studies of VET should include clinically relevant endpoints of bleeding and thrombosis.

Hypercoagulability after injury in premenopausal females: A prospective, multicenter study

Recent studies suggest there are gender-specific differences in injury response that may be related to coagulation. The objective of this study was to test the hypothesis that rapid thrombelastography (rTEG) coagulation profiles differ by gender. Adult trauma patients were prospectively followed at 3 level 1 trauma centers over a 14-month period. rTEG was obtained upon arrival and serially at several time points during the hospital stay. Female patients were stratified into premenopausal (≤50 years) and postmenopausal (>50 years) age groups with age-matched male cohorts. Values were analyzed using a repeated-measures multilevel linear model to evaluate the effect of gender on coagulation. A total of 795 patients had serial rTEG data (24% female and 76% male). Compared with age-matched males, premenopausal females were more hypercoagulable by rTEG on admission (P < .001) and for the first 12 hours after arrival. Gender was an effect modifier for alpha angle (P = .02) and maximum amplitude (P = .04). Controlling for Injury Severity Score and mechanism of injury, age-matched males had a >4-fold increased risk of hypercoagulable complications than premenopausal females (odds ratio, 4.7; P = .038). This prospective, multicenter study demonstrates that premenopausal females are relatively hypercoagulable compared with age-matched males early after injury. However, this did not translate into higher thromboembolic complications.

Hypercoagulability After Injury in Premenopausal Females - A Prospective, Multicenter Study

Background Recent studies suggest there are gender-specific differences in injury response that may be related to coagulation. The objective of this study was to test the hypothesis that rapid thrombelastography (rTEG) coagulation profiles differ by gender. Methods Adult trauma patients were prospectively followed at 3 level 1 trauma centers over a 14-month period. rTEG was obtained upon arrival and serially at several time points during the hospital stay. Female patients were stratified into premenopausal (≤50 years) and postmenopausal (>50 years) age groups with age-matched male cohorts. Values were analyzed using a repeated-measures multilevel linear model to evaluate the effect of gender on coagulation. Results A total of 795 patients had serial rTEG data (24% female and 76% male). Compared with age-matched males, premenopausal females were more hypercoagulable by rTEG on admission (P 4-fold increased risk of hypercoagulable complications than premenopausal females (odds ratio, 4.7; P = .038). Conclusion This prospective, multicenter study demonstrates that premenopausal females are relatively hypercoagulable compared with age-matched males early after injury. However, this did not translate into higher thromboembolic complications.

Platelet activation and platelet–leukocyte interaction in β-thalassemia/hemoglobin E patients with marked nucleated erythrocytosis

Patients with thalassemia, an inherited hemolytic anemia, have increased risk of hypercoagulable complications. A whole blood flow cytometric (FCM) method has been used for studies of platelet activation and platelet-leukocyte aggregation in these patients. However, this FCM method presents technical difficulties because of the high proportion of immature red blood cells (RBCs) in these patients. A protocol for the simultaneous measurement of platelet activation and their aggregation with leukocyte populations in whole blood using four-color FCM which excluded immature RBC was devised, and evaluated for the evaluation of platelet function in patients with β-thalassemia/hemoglobin E (HbE). Whole blood from these patients and from healthy volunteers was stained for platelet activation and platelet-leukocyte aggregates using anti-CD42a, anti-CD62P, anti-CD45 and glycophorin A (GPA) conjugated with different fluorochromes. Our FCM method is simple, effective and based on the assumption that GPA is present on all immature RBCs, but is not expressed on CD45⁺ leukocytes. Results from the studies showed that blood samples from these patients contained a high frequency of circulating activated platelets (CD42a⁺/CD62P⁺) when compared to samples from healthy individuals. The percentage of platelet-neutrophil, platelet-monocyte-but not platelet-lymphocyte-aggregates were also elevated in both thalassemia genotypes with marked increase in patients who had undergone splenectomy. These findings suggest that platelets adhere to neutrophils and monocytes are activated which support the clinical observation that splenectomized thalassemia patients have an increased risk of arterial or venous thrombotic manifestations.

Hemoptysis in TB Endemic Area. Think Again!

This case report illustrates an acute presentation of hemoptysis in a 21-year-old man from a TB endemic region. Further clinical evaluation resulted in extensive hypercoagulability complications of nephritic syndrome due to idiopathic membranous glomerulonephritis (MGN.) This emphasizes that proteinuria seen at a subnephrotic level, or on urine dipstick in a setting where glomerular disease might not be initially apparent, may warrant a keener look.

Antiphospholipid syndrome; its implication in cardiovascular diseases: a review

Antiphospholipid syndrome (APLS) is a rare syndrome mainly characterized by several hyper-coagulable complications and therefore, implicated in the operated cardiac surgery patient. APLS comprises clinical features such as arterial or venous thromboses, valve disease, coronary artery disease, intracardiac thrombus formation, pulmonary hypertension and dilated cardiomyopathy. The most commonly affected valve is the mitral, followed by the aortic and tricuspid valve. For APLS diagnosis essential is the detection of so-called antiphospholipid antibodies (aPL) as anticardiolipin antibodies (aCL) or lupus anticoagulant (LA). Minor alterations in the anticoagulation, infection, and surgical stress may trigger widespread thrombosis. The incidence of thrombosis is highest during the following perioperative periods: preoperatively during the withdrawal of warfarin, postoperatively during the period of hypercoagulability despite warfarin or heparin therapy, or postoperatively before adequate anticoagulation achievement. Cardiac valvular pathology includes irregular thickening of the valve leaflets due to deposition of immune complexes that may lead to vegetations and valve dysfunction; a significant risk factor for stroke. Patients with APLS are at increased risk for thrombosis and adequate anticoagulation is of vital importance during cardiopulmonary bypass (CPB). A successful outcome requires multidisciplinary management in order to prevent thrombotic or bleeding complications and to manage perioperative anticoagulation. More work and reporting on anticoagulation management and adjuvant therapy in patients with APLS during extracorporeal circulation are necessary.

The future of HIV vasculopathy when our patients are on antiretroviral therapy.

South Africa was one of the last countries in Africa to be affected by the HIV epidemic, but currently has one of the highest prevalences in the world. Antiretroviral therapy (ART) was recently introduced in South Africa, and as of December 2007 antiretroviral treatment coverage in this country was about 25% (UNAIDS, 2008). There is a well-documented relationship between vascular disease and HIV infection. This HIV vasculopathy may manifest as arterial aneurysms, occlusive disease or complications of hypercoagulability. The question to be asked is 'What is the future of HIV vasculopathy when our patients are on antiretroviral therapy?'

Association of Thrombosis-Inducing Activity (TIA) With Fatal Hypercoagulable Complications in Patients With Lung Cancer

We previously reported that thrombosis-inducing activity (TIA) is present in plasma from patients with advanced lung cancer. Of 73 patients with non-small cell lung cancer, stages IIIb and IV, 41 (56 percent) had such activity in plasma. The median survival time was significantly shorter in the TIA-positive vs the TIA-negative group. When 34 of those 73 patients who had died at Kyushu University Hospital were evaluated for the incidence of disseminated intravascular coagulation (DIC) and adult respiratory distress syndrome (ARDS), they were significantly higher in the TIA positive group (p < 0.05). The DIC occurred in 7 of 20 patients positive for TIA and 5 died of ARDS. In contrast, in the 14 TIA-negative subjects, only 1 patients experienced DIC and none died of ARDS. Peripheral platelet counts, which had been rather elevated on the day of hospital admission, were below normal within 1 week of death in 40 percent of the 20 patients who were positive for TIA. These observations suggest that TIA may be responsible at least in part for the increased activity of the coagulation system and the high incidence of DIC and ARDS in patients with advanced lung cancer.