Markers of Coagulation Activation and Inflammation in Sickle Cell Disease and Sickle Cell Trait

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4813-4813 ◽  
Author(s):  
Soheir S. Adam ◽  
Galila Zaher ◽  
Mahmoud Ibrahim ◽  
Kenneth I Ataga ◽  
Laura M. De Castro ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Protein C ◽  
Sickle Cell Trait ◽  
Protein S ◽  
T Test ◽  
Cell Disease ◽  
Control Groups ◽  
Coagulation Activation ◽  
And Control ◽  
D Dimer

Abstract It has been well-described that sickle cell disease (SCD) due to HbSS or HbSC is associated with systemic activation of coagulation. A single study has reported a similar, albeit lesser, degree of chronic hyperactivation of coagulation in subjects with sickle cell trait (SCT) (Am J Hem2002; 69(2):89–94), and we have shown that SCT is a risk factor for venous thromboembolism (Blood2007;110(3):908–12). The aim of this study was to simultaneously compare markers of activation of coagulation and inflammation in SCD and SCT. Ninety Saudi Arabian individuals (40 SCD (HbSS), 20 SCT (HbAS) and 30 controls (HbAA)) were recruited. SCD patients were not in vaso-occlusive crisis at the time of sample collection. None of the subjects was taking any relevant medication (anticoagulants, hormones or hydroxyurea), nor had they received blood transfusion for at least 6 weeks. On all subjects, complete blood count (CBC), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer antigen, protein C activity, protein S activity, antithrombin (AT) activity, fibrinogen concentration, activated protein C resistance ratio (APCR), and C-reactive protein (CRP) levels were obtained. Student’s “t” test was used to compare two independent means. Multivariate analysis “ANOVA” test was done to test statistical difference between more than 2 means. Results: D-dimer and CRP were significantly higher, whereas protein C, protein S, and fibrinogen were significantly lower in SS patients compared to controls (Table). In SCT, D-dimer levels were higher, and levels of proteins C and S were significantly lower than controls. APC resistance was more pronounced in both SCD and SCT compared to controls. In summary, this study provides further evidence of hypercoagulability in SCD, but more intriguingly, confirms that significant changes in coagulation parameters may be found in SCT. We speculate that loss of asymmetry of phospholipids in the red cell membrane may occur in certain hypoxic vascular beds (such as the renal vasculature) in SCT. We are currently exploring other possible underlying mechanisms that may contribute to activation of coagulation in SCT. Table: Comparison of Markers of Inflammation and Coagulation Activation in all Groups Group I (SS) (n=40) Group II (AS) (n=20) Group III (AA) (n=30) *P < 0.05 comparing SCD and control groups by paired t- test **P <0.05 comparing SCT and control groups by paired t- test CRP 22.5 ± 10.9* 0.3 ± 0.2 0.3 ± 0.1 PT 12.5 ± 1.6* 12.2 ± 1.0** 11.5 ± 0.6 APTT 33.3 ± 4.2 35.8 ± 4.6** 32.9 ± 3.2 D-dimer 287 ± 140* 278 ± 207** 141 ± 65 Protein C 77.9 ± 20.3* 97.7 ± 21.7** 109.4 ± 17.2 APCR 0.82 ± 0.12* 0.79 ± 0.12** 1.05 ± 0.19 Protein S 54.0 ± 18.4* 64.6 ± 15.4** 89.7 ± 14.9 AT 94.4 ± 16.6* 102.2 ± 7.4** 109.3 ± 10.7 Fibrinogen 305 ± 101 361 ± 146 358 ± 80

Prevalence of Thrombophilia In Patients with Sickle Cell Disease and Osteonecrosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3184-3184
Author(s):  
Murtadha K. Al-Khabori ◽  
Anil Pathare ◽  
Khalil Al Farsi ◽  
Mohammed Al Huneini ◽  
Salam Alkindi
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Protein C ◽  
Dna Analysis ◽  
White Cell Count ◽  
Protein S ◽  
Cell Disease ◽  
High Prevalence ◽  
Low Levels

Abstract Abstract 3184 Background: Osteonecrosis (ON) of the femoral and humeral heads is frequently seen in patients with sickle cell disease (SCD). Earlier studies reported a high prevalence of thrombophilia in patients with ON. Aims: To study the prevalence of thrombophilia in patients of SCD with ON. Methods: Case records of SCD patients with ON were retrospectively reviewed for protein S, protein C, and anti-thrombin deficiency, along with activated protein C resistance (APCR). Results: A total of sixty-three patients were identified, 35 of whom were males, with a median age of 21 years (range 15to 46). Median haemoglobin, total white cell count and platelet counts were 10 g/dL (range 7.7to 13.3), 7.5 ×109/L (range 3.4 to 16.7) and 302 ×109/L (range 72 to 1101) respectively. Twenty-eight patients were on hydroxyurea. Thrombophilia testing showed that 29% (95% confidence interval: 17–40), 47% (95% CI: 29–64) and 79% (95% CI: 65–93) of the patients had low levels of functional (<60 unit/dl), total antigenic (<70 unit/dl) and free antigenic (<70 unit/dl) protein S respectively, while 21% (95% CI: 10–31) and 67% (95% CI: 46–87) had low levels of functional (<70 unit/dl) and antigenic (<70 unit/dl) protein C respectively. In addition, 14% (95% CI: 5–23) and 22% (95% CI: 0–56) of the patients had low levels of functional (<80 unit/dl) and antigenic (<80 unit/dl) anti-thrombin levels respectively. Only 2% (95% CI: 0–5) of these patients had an abnormally low APCR (APCR ratio ≤2.3). Summary/Conclusions: Patients with SCD and ON have a high prevalence of thrombophilia. These results indicate that a prospective study with more detailed thrombophilia work-up, along with confirmatory DNA analysis, as well as a study of the role of prophylactic anticoagulation in such patients is highly warranted. Disclosures: Pathare: Sultan Qaboos University: Employment, Research Funding. Alkindi:Sultan Qaboos University: Employment, Research Funding.

Impact of Erythrocytapheresis on Endogenous Anticoagulants in Sickle Cell Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4590-4590
Author(s):  
Ruchika Sharma ◽  
Gary Woods ◽  
Susan E Creary ◽  
Kan Hor ◽  
Cody Young ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Total Protein ◽  
Research Funding ◽  
Protein C ◽  
Protein S ◽  
Cell Disease ◽  
Educational Grant ◽  
Protein C Activity ◽  
D Dimer ◽  
Protein S Activity

Abstract Introduction The rate of venous thrombo-embolism (VTE) in patients with sickle cell disease (SCD) is estimated to be 4 - 8%; the incidence of catheter-associated VTE in this cohort is 0.16-0.99 per 1000 catheter days. Possible mechanisms for VTE in patients with SCD include hyperviscosity, ischemia reperfusion injury and chronic vascular inflammation. Additionally, patients with SCD exhibit decreased plasma levels of natural anticoagulants such as proteins C and S compared to healthy adults. A retrospective review at our institution found that the incidence of central venous line (CVL)-associated VTE in children with SCD was 0.12/1000 catheter days. On multivariate analysis, CVLs were identified as the only independent risk factor for VTE. Among patients with CVL, we found an association between bilateral CVLs and VTE (Odds Ratio [95% CI] = 10.3 [1.1-92.2]). Children with SCD frequently require CVLs for intravenous access or chronic erythrocytapharesis to reduce SCD-related complications. It is unknown, however, if erythrocytapharesis may also disrupt their natural anticoagulants levels and further increase their risk for subsequent VTE. We hypothesized that erythrocytapheresis may contribute to the pro-coagulant phenotype by altering patients' natural anticoagulants levels. Methods As part of a quality improvement initiative we measured antithrombin (AT), protein C antigen and activity, protein S antigen (total and free) and activity prior to being placed on the apheresis circuit and after completion of exchange in patients with SCD (0-21 years of age) undergoing chronic erythrocytapheresis who had a CVL (between January 1, 2009 and January 31, 2015). D-Dimer levels were obtained pre exchange only. Protein C and S levels were measured using ELISA based assays; protein C and S activities were measured using a clotting based assay and AT was measured using a chromogenic assay. The resulting levels, pre and post-erythrocytapheresis were analyzed using a paired nonparametric Wilcoxon rank test. Results Eleven patients were eligible for this study (8 females, 3 males). Median age at the time of erythrocytapheresis was 14 years (±3.65 SD) years. Indications for erythrocytapheresis included primary/ secondary stroke prevention or recurrent acute chest syndrome. All patients had bilateral CVLs in place. Four of the included patients had a history of VTE; 2 patients were on anticoagulation with low molecular weight heparin at the time of the study. The mean value for total protein S antigen (65u/dL; normal >72u/dL), free protein S antigen (53u/dL; normal >70u/dL), and protein S activity (51IU/mL; normal 65-138IU/ml) were all abnormal pre- erythrocytapheresis and decreased significantly following erythrocytapheresis (52u/dL, 44u/dL, and 44IU/mL respectively). Mean protein C antigen (71u/dL; normal >55u/dL), protein C activity (71%; normal 55-111%), and AT activity (104%; normal 77-132%) were within the normal range pre-erythrocytapheresis and decreased significantly post-erythrocytapheresis. We demonstrated significantly lower levels of protein C antigen (p=0.01), protein C activity (p=0.01), total protein S antigen (p=0.005), free protein S antigen (p=0.036), protein S activity (p=.04), and AT activity (p=.004) following erythrocytapheresis (Figure). D-Dimer levels were elevated in 6/11 patients (54.5%). Conclusions Pre- and post-erythrocytapheresis levels of natural endogenous anticoagulants investigated in a cohort of patients with SCD undergoing chronic erythrocytapheresis demonstrated that levels of all investigated proteins were significantly lower in patients following erythrocytapheresis. D-dimer levels were elevated in the majority of patients pre exchange but the importance of this finding is unclear. Given the relatively short half-life of the natural anticoagulants (2-3 hours for protein C and 36-60 hours for AT and protein S), it is unclear if this acute decrease of natural anticoagulants is clinically relevant. Further investigation is needed to determine if this acute decrease may contribute to an increased VTE risk in children with SCD undergoing apheresis. Figure 1. Figure 1. Disclosures Woods: Biogen: Other: Educational Grant. Dunn:Novo Nordisk: Consultancy, Other: Educational Grant; CSL Behring: Consultancy, Other: Data Safety Monitoring Board; Bayer: Consultancy, Other: educational grant; Biogen: Consultancy, Other: Educational grant, Research Funding; Baxalta: Consultancy, Other: educational grant, Research Funding; Ohio State University: Employment; Pfizer: Other: Grant Review Board.

scholarly journals Protection of Microvascular Liver Perfusion with 5-Hydroxymethylfurfural in Sickle Cell Disease Mice Following Hypoxia-Induced Vasoocclusion

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3382-3382 ◽  
Author(s):  
Michael Wright ◽  
Derek Sim ◽  
Magdalena Alonso-Galicia ◽  
Katalin Kauser ◽  
Keith Abe
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Genetic Disorder ◽  
Liver Perfusion ◽  
Organ Damage ◽  
Extramedullary Hematopoiesis ◽  
T Test ◽  
Vehicle Group ◽  
Cell Disease ◽  
And Control

Abstract Introduction: Sickle cell disease (SCD) is a debilitating genetic disorder, and the resultant "sickling" deformity of red blood cells leads to acute vasoocclusive (VOC) events and chronic disease in multiple organs. Sickle cell hepatopathy, arising from VOC events in the hepatic sinusoids, which can lead to fatal sickle cell intrahepatic cholestasis, is estimated to occur in approximately 10% of the SCD population. Using contrast-enhanced ultrasound (CEUS), we measured microvascular liver perfusion (MVLP) in SCD and control mice at basal levels to determine if noninvasive CEUS can be utilized to assess the underlying extent of disease and also investigated the effect of hypoxia-induced VOC with and without treatment with an antisickling agent, 5-hyroxymethylfurfural (5-HMF). Methods: Townes sickle cell mice (SCD), homozygous for hα:βs -globulin, approximately 7−9 weeks of age (n=28), and control mice, homozygous for hα:β-globulin (n=11), were used in these studies. CEUS perfusion imaging (Vevo® 2100) was performed on a central cross-section of the liver at the renal artery. Contrast agent was administered as an intravenous bolus via tail vein to anesthetized mice (isoflurane with ~21% O2); peak enhancement (PE) was analyzed with VisualSonics software. CEUS measurements were obtained at baseline and following either (1) hypoxia, 60 minutes with 5.5.% O2 followed by ~60 minutes of reoxygenation at room oxygen (~21% O2) or (2) normoxia, ~120 minutes at room oxygen. 5-HMF at 20 and 200 mg/kg PO or vehicle was administered following baseline PE measurement and approximately 30 minutes before start of hypoxia. Results: MVLP in SCD (n=28) was significantly reduced by approximately 40% compared with controls (n=11) at baseline (PE of 14.0±0.7 linear arbitrary units [l.a.u.] vs. 23.6±2.1 l.a.u.), respectively, P<0.001 [Student t test]). Normoxic SCD maintained similar PE to baseline levels (Table 1); however, hypoxia significantly reduced MVLP by 49% in SCD mice. In contrast, hypoxia had no significant effect in control mice. 5-HMF at 20 and 200 mg/kg resulted in a dose-dependent increase in posthypoxia MVLP. 5-HMF at 200 mg/kg was not significantly different from baseline PE, and 5-HMF at 20 mg/kg increased MVLP by approximately 50% compared with the vehicle group posthypoxia (26% vs 49% reduction in MVLP, respectively). Pathologic evaluation of naive SCD formalin-fixed liver tissues (n=10) showed congestion, necrosis, hepatocellular hypertrophy, and extramedullary hematopoiesis. Table 1. CEUS-Acquired Microvascular Liver Perfusion in SCD and Control Mice (mean ± SEM) Strain Dose Oxygen Status Mice, n Baseline PE, l.a.u. Posthypoxia/Normoxia PE, l.a.u. Change From Baseline, % Control Vehicle Hypoxic 11 23.6±2.1 22.1±2.1 -7 SCD Vehicle Normoxic 4 14.0±2.1 13.3±1.6 -3 SCD Vehicle Hypoxic 8 15.4 ±1.6 7.0±0.9* -49 SCD HMF, 20 mg/kg Hypoxic 8 12.8±0.9 9.2±0.7* -26 SCD HMF, 200 mg/kg Hypoxic 8 13.8±1.5 11.9±1.2 -12 *Statistically significant reduction compared with baseline PE (P <0.01, Student t test). Summary: CEUS measured lower basal levels of MVLP in SCD compared with control mice, which correlated with pathologic findings of congestion and necrosis in the livers of SCD mice. The hypoxia-induced VOC decrease in MVLP was present only in the SCD mice; no effect was observed in control mice. Treatment with the antisickling agent, 5-HMF, dose-dependently ameliorated the hypoxia-induced VOC decrease in MVLP in SCD mice. Based on these results, CEUS may be considered as a noninvasive method to measure acute and chronic organ perfusion changes for evaluating new therapeutics for sickle cell-mediated VOC events and end-organ damage. Disclosures Wright: Bayer HealthCare LLC: Employment. Sim:Bayer HealthCare LLC: Employment. Alonso-Galicia:Bayer HealthCare LLC: Employment. Kauser:Bayer HealthCare LLC: Employment. Abe:Bayer HealthCare LLC: Employment.

scholarly journals Protein C and protein S in homozygous sickle cell disease: does hepatic dysfunction contribute to low levels?

1997 ◽  
Vol 98 (3) ◽  
pp. 627-631 ◽  
Author(s):  
J. G. Wright ◽  
R. Malia ◽  
P. Cooper ◽  
P. Thomas ◽  
F. E. Preston ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Protein C ◽  
Hepatic Dysfunction ◽  
Protein S ◽  
Cell Disease ◽  
Low Levels ◽  
Homozygous Sickle Cell Disease

scholarly journals Mortality and Access to Kidney Transplantation in Patients with Sickle Cell Disease–Associated Kidney Failure

2021 ◽  
pp. CJN.02720320
Author(s):  
Sunjae Bae ◽  
Morgan Johnson ◽  
Allan B. Massie ◽  
Xun Luo ◽  
Carlton Haywood ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Sickle Cell Disease ◽  
Confidence Interval ◽  
Sickle Cell ◽  
Kidney Failure ◽  
Absolute Risk ◽  
Hazard Ratio ◽  
Cell Disease ◽  
Control Groups ◽  
And Control

Background and objectivesPatients with sickle cell disease–associated kidney failure have high mortality, which might be lowered by kidney transplantation. However, because they show higher post-transplant mortality compared with patients with other kidney failure etiologies, kidney transplantation remains controversial in this population, potentially limiting their chance of receiving transplantation. We aimed to quantify the decrease in mortality associated with transplantation in this population and determine the chance of receiving transplantation with sickle cell disease as the cause of kidney failure as compared with other etiologies of kidney failure.Design, setting, participants, & measurementsUsing a national registry, we studied all adults with kidney failure who began maintenance dialysis or were added to the kidney transplant waiting list in 1998–2017. To quantify the decrease in mortality associated with transplantation, we measured the absolute risk difference and hazard ratio for mortality in matched pairs of transplant recipients versus waitlisted candidates in the sickle cell and control groups. To compare the chance of receiving transplantation, we estimated hazard ratios for receiving transplantation in the sickle cell and control groups, treating death as a competing risk.ResultsCompared with their matched waitlisted candidates, 189 transplant recipients with sickle cell disease and 220,251 control recipients showed significantly lower mortality. The absolute risk difference at 10 years post-transplant was 20.3 (98.75% confidence interval, 0.9 to 39.8) and 19.8 (98.75% confidence interval, 19.2 to 20.4) percentage points in the sickle cell and control groups, respectively. The hazard ratio was also similar in the sickle cell (0.57; 95% confidence interval, 0.36 to 0.91) and control (0.54; 95% confidence interval, 0.53 to 0.55) groups (interaction P=0.8). Nonetheless, the sickle cell group was less likely to receive transplantation than the controls (subdistribution hazard ratio, 0.73; 95% confidence interval, 0.61 to 0.87). Similar disparities were found among waitlisted candidates (subdistribution hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72).ConclusionsPatients with sickle cell disease–associated kidney failure exhibited similar decreases in mortality associated with kidney transplantation as compared with those with other kidney failure etiologies. Nonetheless, the sickle cell population was less likely to receive transplantation, even after waitlist registration.

The evidence base for the risk and management of thrombosis in hematological malignancies patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 16526-16526
Author(s):  
F. M. Hassan
Keyword(s):  
Protein C ◽  
Hematological Malignancies ◽  
Oral Anticoagulants ◽  
Age Groups ◽  
Protein S ◽  
Clinical Analysis ◽  
Lymphoid Tissues ◽  
Control Groups ◽  
S Protein ◽  
D Dimer

16526 Background: To evaluate of hypercoagulable state and tumor procoagulant activity in hematological malignancies patients.To address the Primary thromboprophylaxis managed. Methods: Paper-based reply-paid questionnaire was distributed between patients, included the information about the duration, treatment used, sex, age, and type of malignant. We respectively analyzed 96 Patients male and female in all age groups treated for the prevention of recurrent venous thromboembolism in patients with hematological malignancies patients, against 33 (19–75 years, 15 male, 18 female) apparently healthy adults individual setting as control groups. The clinical analysis included thrombotic markers (protein S, protein C, PF1.2, TAT, PAI-1and fibrin D-dimer) were done to all patients and control. Low-molecular weight heparin (LMWH) versus Oral anticoagulant frequency distribution were compared between cases and controls using statistical analysis. Results: In total, 93 completed questionnaires were returned, respondents were reported the routine treatment of more than 10 types of haemopatopoietic and lymphoid tissues tumours. Of these, CML and CLL were most commonly treated (by 45%-62% of respondents), with lymphoma, plasma cell myeloma, AML, polythycythemia vera, and mast cell sarcoma the next most common (treated by 26%-38% of respondents). Most of patients (76%) showed a markedly elevation of PAI-1 and D-dimer and significantly elevated in whose treated Surgically, while the other thrombotic markers (protein S, protein C, PF1.2, TAT were normal compared to control groups. Conclusions: Thrombosis is a common complication in patients with haemopatopoietic and lymphoid tissues tumours that adversely affects their survival. There are several problems associated with the treatment of VTE in patients, especially with the use of oral anticoagulants. No significant financial relationships to disclose.

scholarly journals Vascular endothelial dysfunction in sickle cell disease by brachial artery flow mediated dilatation

2014 ◽  
Vol 5 (3) ◽  
pp. 105-107 ◽  
Author(s):  
Pranav Kumar Raghuwanshi ◽  
Somnath Singh Raghuvanshi
Keyword(s):  
Endothelial Dysfunction ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Control Group ◽  
Cell Disease ◽  
Significant Difference ◽  
Flow Mediated Dilatation ◽  
Artery Flow ◽  
And Control

Objective: The present study was conducted aiming to assess endothelial function in sickle cell disease (SS), sickle cell trait(SA) and compare to endothelial dysfunction between sickle cell anemia (SS), sickle cell trait (SA) cases and control (AA) patients to evaluate correlation of endothelial dysfunction. Methods: The study population comprised of, total 25 cases having sickle cell disease and sickle cell trait and 25 age and sex matched normal control. Endothelial dysfunction as assessed by brachial artery flow mediated dilatation by colour Doppler (non-invasive method)by using Siemens Sonoline 500. Statistical analysis was performed using Software Statistical Package for Social Sciences (SPSS) version 20, and P value of less than 0.05 was considered as statistically significant at 95% confidence intervals. Results: Significant difference were observed in FMD (flow mediated vasodilatation) in case and control group (p<0.05), also significant difference was demonstrated between AS and SS group. Conclusion: The percentage of flow mediated dilatation of vessel is a marker of endothelial function was significantly lower in cases as compared to controls and was also lower in AS & SS when compared to control group & significantly lower in SS group than AS group. Asian Journal of Medical Science, Volume-5(3) 2014: 105-107 http://dx.doi.org/10.3126/ajms.v5i3.9445

Thromboelastographic Characterization of the Activated Clotting System in Children with Sickle Cell Trait or Sickle Cell Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3809-3809
Author(s):  
Shveta Gupta ◽  
Roxana Carmona ◽  
Jemily Malvar ◽  
Guy Young
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Cells ◽  
Thrombin Generation ◽  
Sickle Cell Trait ◽  
Coagulation System ◽  
Cell Disease ◽  
D Dimer

Abstract Background: Recent epidemiological evidence suggests sickle cell disease (SCD) and sickle cell trait (SCT) are risk factors for venous thromboembolism. The increased in vivo markers of thrombin generation support the notion that such patients are in a chronic hypercoagulable state. In an attempt to better understand the underlying mechanism, global hemostatic assays including thrombin generation assay (TGA) and thromboelastography (TEG) have been utilized by several groups, with inconsistent results either due to small sample size or technical differences. As opposed to the bleeding disorders, the traditional methods of TEG are not sensitive to hypercoagulability. Our group developed modified methods that prolonged the baseline TEG parameters to enhance this sensitivity. These altered TEG profiles were shown to be significantly shortened by increasing concentrations of thrombin in vitro. Objectives: Global hemostatic characterization of children with SCD or SCT by using TGA and modified TEG methods. Materials and methods: In this pilot study, we obtained hemostatic data including complete blood count with differential, reticulocyte count, fibrinogen, D-dimer, thrombin antithrombin complex and prothrombin fragment 1.2 on specimens from subjects with SCD in their usual state of health, subjects with SCT and healthy controls (NC). In addition global hemostatic assays including standard and modified thromboelastography methods as well as thrombin generation assays were performed. Results: Thirty-nine African-American subjects were recruited: 12 NC, 14 SCT and 13 SCD. The median ages for the groups were 12 (Range: 5-39), 19 (Range: 2-40) and 8 (Range: 2-14) years for NC, SCT, and SCD, respectively. Females represented 58% of the NC, 57% of the SCT subjects and 38% of the SCD subjects. In vivo markers of thrombin generation and activation of fibrinolysis including D-dimer and thrombin-antithrombin complexes were higher in SCD subjects as compared to SCT and NC (p=0.001; p=0.05 respectively). Reaction (R) time, and Kinetic (K) time with modified TEG methods was significantly shorter in SCD when compared to SCT and NC (p=0.014, p=0.038) respectively. Angle (alpha) and maximum amplitude (MA) did not show any significant differences between the groups. TGA profiles did not show any difference between the three groups either. Conclusion: The in vivo use of modified thromboelastography methods is able to detect the hypercoagulability known to occur in the sickle cell disease population but a larger sickle cell trait cohort needs to be studied to determine if this group also has hypercoagulability. Importantly, this study, the first to evaluate both TEG and TGA assays in SCD or SCT population demonstrates the importance of using whole blood to differentiate these groups as the TEG assay demonstrated differences the TGA could not detect. As SCD and SCT subjects have a highly complex physiology with not only alterations in almost all the components of the coagulation system, but also variation in the quantity and function of other blood components including white blood cells, platelets and red blood cells, TEG may prove a good tool in measuring a change in the activity of the coagulation system rather than a single baseline measurement. Our results support the need for further studies using thromboelastography in SCD and SCT population in order to better understand and triage this cohort of patients for risks of thrombotic complications. Disclosures No relevant conflicts of interest to declare.

APC Resistance and other Haemostatic Variables during Pregnancy and Puerperium

1999 ◽  
Vol 81 (04) ◽  
pp. 527-531 ◽  
Author(s):  
U. Kjellberg ◽  
N.-E. Andersson ◽  
S. Rosén ◽  
L. Tengborn ◽  
M. Hellgren
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Protein C ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Reference Level ◽  
Soluble Fibrin ◽  
Prothrombin Fragment ◽  
D Dimer

SummaryForty-eight healthy pregnant women were studied prospectively and longitudinally. Blood sampling was performed at 10-15, 23-25, 32-34 and 38-40 weeks of gestation, within one week and at eight weeks postpartum. Classic and modified activated protein C ratio decreased as pregnancy progressed. In the third trimester 92% of the ratios measured with the classic test were above the lower reference level whereas all modified test ratios were normal. Slight activation of blood coagulation was shown with increased levels of prothrombin fragment 1+2, soluble fibrin and D-dimer. Fibrinogen, factor VIII and plasminogen activator inhibitor type 1 and type 2 increased. Protein S and tissue plasminogen activator activity decreased. Protein C remained unchanged. No correlation was found between the decrease in classic APC ratio and changes in factor VIII, fibrinogen, protein S, prothrombin fragment 1+2 or soluble fibrin, nor between the increase in soluble fibrin and changes in prothrombin fragment 1+2, fibrinogen and D-dimer.

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