Extensive Characterization of the Hemostatic Derangement Occurring in COVID-19 Patients Admitted to the Bergamo Hospital

INTRODUCTION The occurrence of a hypercoagulable state in hospitalized COVID-19 patients is supported by studies conducted with routine coagulation tests, including plasma D-dimer and fibrinogen, and platelet count. AIM In this study we performed an extensive characterization of the hemostatic alterations by both global and specific assays in a cohort of 78 patients hospitalized for COVID-19. The aims were to: 1) clarify mechanisms underlying the coagulopathy, and 2) identify predictive factors of disease severity and thrombotic events (i.e. deep vein thrombosis [DVT], pulmonary embolism [PE] or arterial thromboembolism [ATE]). METHODS COVID-19 patients admitted to the Hospital Papa Giovanni XXIII in Bergamo, Italy, from March 23 to May 30, 2020, were enrolled prospectively, providing informed consent. As a global assay, thromboelastometry (ROTEM) was performed in whole blood by EXTEM, INTEM, and FIBTEM tests. Specific assays included plasma levels of intrinsic and extrinsic pathway coagulation factors, von Willebrand factor (vWF) antigen and activity, anticoagulant proteins (i.e. protein C [PC], free-protein S [PS], and antithrombin [AT]), fibrinolytic proteins (i.e. tissue plasminogen activator [t-PA], and inhibitor [PAI-1]), and hypercoagulation biomarkers (i.e. prothrombin fragment 1+2 [F1+2], and D-dimer). In addition, biomarkers of immunoinflammation (i.e. neutrophil extracellular traps [NETs], CRP and procalcitonin) were measured. Occurrence of thrombotic events and death were monitored during follow up. RESULTS 78 patients (56M/22F), median age 62.7 years (25-87), were analyzed. According to disease severity, 45 were ICU, and 33 non-ICU patients. Sixty-three of them were on thromboprophylaxis. Global hemostasis analysis by ROTEM showed a prothrombotic profile in patients compared to controls, with a significantly shorter clot formation time (CFT), and increased maximum clot firmness (MCF), which were significantly greater in the ICU vs non-ICU patients. The occurrence of an 'in vivo' hypercoagulable state was confirmed by increased plasma levels of F1+2 and D-dimer, with the highest values of D-dimer in the ICU subjects. Hypercoagulability, rather than factors' consumption, was also shown by the findings of significantly higher plasma procoagulant factors V, VIII, IX and fibrinogen in ICU compared to non-ICU patients (p<0.001). Endothelium activation was shown by extremely elevated vWF antigen and activity levels in all patients (highest values in ICU subjects). Moreover, the concentrations of fibrinolytic proteins, t-PA, and its inhibitor PAI-1, were elevated (p<0.01) in patients compared to normal controls, without difference between ICU and non-ICU subjects. Finally, the inflammatory parameters' analysis in the ICU group demonstrated significantly increased plasma levels of NETs, CRP, and procalcitonin, compared to non-ICU patients. Of note, NETs levels significantly (p<0.02) correlated with vWF, D-dimer and t-PA, while CRP and procalcitonin inversely correlated with anticoagulant PC. After a median time of 8.8 days, 19 (24%) patients experienced thrombosis (3 DVT, 8 PE, 8 ATE). Thirteen (17%) patients from total population died after a median time of 33 days of hospitalization. Baseline D-dimer and t-PA levels were significantly higher in patients developing VTE, while baseline FVIII, vWF and D-dimer levels were greater in subjects who died during follow-up. By Cox analysis, high D-dimer and younger age were significantly associated with mortality. CONCLUSIONS Our study provides for the first time an extensive overview of the hypercoagulable state induced by SARSCoV-2 infection, demonstrating alterations in all of the different hemostatic compartments analyzed. The viral infection-induced hemostatic abnormalities are exacerbated by the severity of the disease and strongly correlate with the proinflammatory status, demonstrating the link between coagulation and inflammation. This link is further supported by the clear correlation found between NETosis and markers of endothelial and blood clotting activation. Finally, these data add evidence to the role of D-dimer as a significant predictor of intra-hospital mortality. Disclosures No relevant conflicts of interest to declare.

Download Full-text

One Month Follow-up of Haemostatic Variables in Patients Undergoing Aortocoronary Bypass Surgery

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653780 ◽

1995 ◽

Vol 73 (03) ◽

pp. 356-361 ◽

Cited By ~ 23

Author(s):

L Mannucci ◽

P S Gerometta ◽

L Mussoni ◽

C Antona ◽

A Parolari ◽

...

Keyword(s):

Cardiopulmonary Bypass ◽

Bypass Surgery ◽

Fibrinolytic System ◽

Aortocoronary Bypass ◽

Protamine Sulphate ◽

Aortocoronary Bypass Surgery ◽

Intraoperative Period ◽

Pai 1 ◽

D Dimer

SummaryIt is already known that activation of the coagulation and fibrinolytic system occurs in patients undergoing cardiopulmonary bypass (CPB). We have thus studied twenty patients (10 treated with aprotinin during CPB and 10 untreated) both during the intraoperative period and during thirty days follow up. In untreated patients D-dimer levels increased 4-fold during CPB and the levels were above baseline for the whole follow up (p<0.0001). D-dimer levels were reduced in aprotinin treated patients in comparison to untreated patients (p = 0.0172); levels then gradually increased to the values of the untreated patients over the following 24 h later and remained higher during the thirty day follow up. The behavior of haemostatic variables in the 24 h after CPB did not vary between untreated and aprotinin treated patients. In particular, five minutes after protamine sulphate administration, levels of F1 + 2 and TAT rose significantly (p = 0.0054, p = 0.0022 respectively), whereas fibrinogen significantly decreased (p<0.0001) and PAI-1 antigen levels were reduced. Two days after CPB the concentrations of F1 + 2 and TAT lowered, whereas fibrinogen and PAI-1 antigen levels increased. On the 5th, 8th and 30th days after CPB, F1 + 2 and TAT levels remained higher than those reported at baseline in both groups of patients, whereas fibrinogen levels increased over basal levels in aprotinin treated patients only.Thus, in addition to the activation of the coagulation and fibrinolytic system occurring during the intraoperative period, in patients undergoing CPB, there are alterations of haemostatic variables up to thirty days from surgery.

Download Full-text

Abstract P663: Polygenic Risk Scores for Plasma Levels of Fibrin D-Dimer and Tissue Plasminogen Activator Are Associated With Non-Lacunar Stroke

Stroke ◽

10.1161/str.52.suppl_1.p663 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Yonit A Addissie ◽

Brady Gaynor ◽

Thomas Jaworek ◽

Huichun Xu ◽

Colin O Stine ◽

...

Keyword(s):

Ischemic Stroke ◽

Plasma Levels ◽

Early Onset ◽

Late Onset ◽

Plasma Concentrations ◽

Risk Scores ◽

Lacunar Stroke ◽

Related Factors ◽

Pai 1 ◽

D Dimer

Introduction: Plasma concentrations of prothrombotic factors such as fibrinogen have previously been associated with ischemic stroke risk. To extend this observation, we examined the association of polygenic risk scores (PRS) for increased plasma levels of thrombosis-related factors with ischemic stroke. Our hypotheses were that these PRS would be more associated with early than late onset stroke and with non-lacunar than lacunar stroke. Methods: We identified 9053 late onset (≥ 60 years) stroke cases from the NINDS International Stroke Genetics Consortium (SiGN) with 24804 controls and 6594 early onset (< 60 years) stroke cases from the Genetics of Early Onset Ischemic Stroke Consortium with 30561 controls. We identified previously known loci associated with plasma levels of four thrombosis-related factors: fibrinogen, fibrin D-dimer, tPA and PAI-1 from prior GWAS studies and developed genome-wide PRS for plasma concentrations of these factors. We then used logistic regression to test the association of these scores with risk of stroke and stroke subtype. Results: PRS for fibrin D dimer levels were associated with increased risk for all stroke and specifically for older (p = 0.019), but not younger (p = 0.22) onset stroke. PRS for tPA levels were also marginally associated with older (p = 0.06), but not younger (p = 0.24) onset stroke. Genetic risk scores for both D dimer and tPA were associated with non-lacunar stroke (Table 1). Further analyses stratified by age revealed PRS for D dimer to be significantly associated with non-lacunar stroke (but not lacunar stroke) in both late and early onset cohorts. PRS for fibrinogen and PAI-1 were not associated with stroke. Conclusion: Genomic risk scores for thrombosis-related factors including D dimer and tPA levels were associated with risk for ischemic stroke, and specifically, non-lacunar stroke.

Download Full-text

RISK OF RECURRENT THROMBOTIC EVENTS IN PATIENTS WITH ACUTE CORONARY SYNDROME AND HIGH PLASMA LEVELS OF D-DIMER

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2013-4-26-31 ◽

2013 ◽

Vol 12 (4) ◽

pp. 26-31

Author(s):

A. V. Panina ◽

N. F. Puchinyan ◽

Ya. P. Dovgalevskyi ◽

N. V. Furman ◽

P. V. Dolotovskaya ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Plasma Levels ◽

Coronary Care Unit ◽

Fold Increase ◽

High Plasma ◽

Additional Risk ◽

Coronary Syndrome ◽

Coronary Care ◽

D Dimer

Aim. To study the association of plasma D-dimer levels and the risk of thrombotic events in patients hospitalised with acute coronary syndrome (ACS).Material and methods. The study included 70 patients, aged 34-88 years, who were admitted to the Acute Coronary Care Unit with the ACS diagnosis.Results. During the follow-up period, thrombotic events were registered in 12 patients (17%). Three patients with myocardial infarction (MI) suffered recurrent MI. Nine patients were rehospitalised with the unstable angina (UA) diagnosis. All participants were divided into quartiles by the levels of D-dimer (25% percentile 136 ng/ml; median 1250 ng/ml; and 75% percentile 2930 ng/ml). High plasma levels of D-dimer (third quartile) were associated with a 1,5-fold increase in the risk of recurrent thrombotic events among ACS patients.Conclusion. In ACS patients, plasma D-dimer levels could be regarded as one of the additional risk factors of thrombotic events.

Download Full-text

Laboratory manifestations of COVID-19 associated with hemostatic abnormalities

Journal of Ideas in Health ◽

10.47108/jidhealth.vol4.iss3.133 ◽

2021 ◽

Vol 4 (3) ◽

pp. 423-427

Author(s):

Ahmed Elhadi Elsadig ◽

May Mohammed Ali ◽

Alfatih Aboalbasher Yousif

Keyword(s):

Disease Severity ◽

Protein C ◽

Degradation Products ◽

Disease Outcome ◽

Icu Patients ◽

Fibrin Degradation Products ◽

Laboratory Markers ◽

Increased Risk ◽

Coagulation Tests ◽

D Dimer

Hemostatic abnormalities had been reported in COVID-19 patients, which may include disseminated intravascular coagulation (DIC), hypercoagulability, and alterations in platelets parameters. Articles that investigate the alterations of hemostatic abnormalities during the COVID-19 disease (2020-2021) and their predictive value of disease outcome have been thoroughly reviewed. Among the reviewed articles, thrombocytopenia is observed in 5.0-41.7% of COVID-19 patients, which is related to disease severity. Moreover, other platelets parameters, including Platelets/lymphocytes ratio (PLR), Mean platelets volume (MPV), and aggregation, may also be affected. On the other hand, findings of coagulation tests such as D dimer; fibrinogen, Antithrombin (AT), and Fibrin degradation products (FDP) are significantly elevated in COVID-19 patients, while in a single study, most of the patients had positive Lupus anticoagulants (LA) and normal protein C (PC). In the same perspective, these alterations showed significant correlations with disease severity. Overall, hemostatic laboratory markers are significant predictors of COVID-19 disease outcome as indicated by the increased risk of venous and arterial thrombotic events, especially in ICU patients.

Download Full-text

Relationship of plasma levels of sICAM-1, TNF-α and D-dimer with disease severity in patients with acute pancreatitis

World Chinese Journal of Digestology ◽

10.11569/wcjd.v18.i32.3480 ◽

2010 ◽

Vol 18 (32) ◽

pp. 3480

Author(s):

Chun-Yan Li ◽

Gui-Zhen Yong ◽

Ying-Chun Feng ◽

Guo-Bin He ◽

Jun-Ying Xiang ◽

...

Keyword(s):

Acute Pancreatitis ◽

Disease Severity ◽

Plasma Levels ◽

Tnf Α ◽

Relationship Of ◽

D Dimer

Download Full-text

Endothelial Activation, FVW and ADAMTS 13 imbalance and Fibrinolysis Impairment in Adults with Dengue Fever with Bleeding Complications,

Blood ◽

10.1182/blood.v118.21.3325.3325 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3325-3325

Author(s):

Fernanda A. Orsi ◽

Bruna m Mazetto ◽

Rodrigo Angerami ◽

Erich V De Paula ◽

Joyce Annichino-Bizzachi

Keyword(s):

Vascular Permeability ◽

Dengue Fever ◽

Plasma Levels ◽

Endothelial Activation ◽

Adult Patients ◽

Fluid Replacement ◽

Bleeding Complications ◽

Tnf Alpha ◽

Pai 1 ◽

D Dimer

Abstract Abstract 3325 Dengue fever has enormous health and economic impact in Latin America, Africa, India and Southeast Asia. In Brazil, an increasing number of severe cases of dengue have been notified, especially those with bleeding complications. Classically, the bleeding episodes in dengue have been attributed to an increased vascular permeability, but in many cases there is no evidence of vascular changes that justify the clinical bleeding. Several coagulation disorders may contribute to the occurrence of bleeding complications in dengue and knowledge of these disorders can lead to more specific treatment of the disease, in addition to conventional treatment based on fluid replacement. The aim of this study is to evaluate how the different homeostatic mechanisms behave in adults with complicated dengue fever, focusing on the modulators of capillar permeability, VWF, ADAMTS 13 and fibrinolysis parameters, correlating them with the clinical presentation of disease. Patients and methods: We recruited patients with the diagnosis of complicated dengue fever between March and May 2008 in the General Hospital of Ipanema, in Rio de Janeiro, and in the Clinical Hospital of UNICAMP, in Campinas. Alongside healthy individuals were recruited as controls. The analysis of plasma levels of VWF, tPA, D-dimer, TNF-alpha, thrombomodulin and PAI-1 were performed by ELISA. The ADAMTS 13 activity was quantified by residual binding of VWF to collagen. Results: We included 35 adult patients with dengue complicated by bleedings (DCB) and 50 controls. The diagnosis of dengue hemorrhagic fever (DHF) was done only in three patients who had pleural effusion, the other cases had no clinical signs of increased vascular permeability, the criteria for the diagnosis of DHF. The group of patients with DCB presented,comparing to controls, increased levels of VWF (median = 244.1 vs. 136.9 U/ml, P <0.0001), decreased ADAMTS13 activity (median = 72.4 vs. 125 7%, P <0.0001), increased TNF-alpha (median 2.35 vs. 1.90 pg/ml, P = 0.038), increased thrombomodulin (median 6.15 vs. 4.79 ng/ml, P = 0.0003), increased tPA antigen (median 10.8 vs. 4.2 ng/ml, P <0.0001) and increased D-dimer plasma levels (median 1745 versus 478ng/ml, P <0.0001). There was no statistical difference between patients and controls with regard to the serum levels of VEGF (median = 34.8 vs. 19.1 pg/ml) and plasma levels of PAI-1 (median = 7.4 vs. 6.5 U/ml). We also performed correlation analyzes between the different parameters studied. Thus, we found that the platelet count was indirectly correlated with plasma levels of tPA (r = −0.3432, 95% CI = −0.5921 to −0.03451, P = 0.0261) and D-dimer (r = −0.3996, 95% CI = −0.6381 to −0.09112, P = 0.0106). Conclusion: The increased plasma levels of VWF, tPA and thrombomodulin suggest a possible endothelial activation in patients with DCB, followed by stimulation of fibrinolysis. The activation of fibrinolysis in dengue fever have been described in children patients previously. Interestingly, normal levels of VEGF in these patients with DCB suggest that there is no impairment in vascular permeability in these cases. Then, fibrinolysis and thrombocytopenia seems to be the main causes of bleeding in this study. Patients with moderate to severe thrombocytopenia had the highest plasma levels of tPA and D-dimer, thus suggesting that increased levels of these proteins could be related to disease severity in adult patients. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Hemostatic Alterations in Patients with Acute, Unilateral Vestibular Paresis

Otolaryngology ◽

10.1067/mhn.2001.114795 ◽

2001 ◽

Vol 124 (4) ◽

pp. 401-407 ◽

Cited By ~ 11

Author(s):

Bruno Fattori ◽

Andrea Nacci ◽

Augusto Casani ◽

Renza Cristofani ◽

Andrea Sagripanti

Keyword(s):

Prothrombin Time ◽

Acute Phase ◽

Plasma Levels ◽

Protein C ◽

Leukocyte Count ◽

Blood Parameters ◽

Ménière’S Disease ◽

Lipoprotein A ◽

D Dimer

OBJECTIVES: The etiopathogenesis of acute unilateral peripheral vestibulopathy (APV) still remains a matter of debate; ischemic changes in the circulation of the labyrinth may play a role. We consequently looked for possible hemostasis alterations in a group of patients with APV of an unknown nature. METHODS: We evaluated blood parameters known to be involved in circulation disorders, including total and HDL cholesterol, tryglycerides, apolipoprotein A and B, lipoprotein(a), homocysteine, folate, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, antithrombin III, protein C, protein S, activated protein C resistance, and anticardiolipin IgG and IgM antibodies. A series of 23 patients affected with APV were consecutively referred to our department, in the acute phase, before treatment, and in the follow-up phase after 4 to 6 weeks of pharmacologic washout. The aforementioned blood parameters were also measured in a series of 15 patients with Menière's disease. RESULTS: The patients with APV in the acute phase compared with the patients with Menière's disease in the acute phase exhibited increased plasma levels of fibrinogen (mean, 338.3 ± 135.9 SD vs 271.3 ± 69.8 SD mg/dL, P = 0.05), increased plasma levels of D-dimer (mean, 320 ± 207.8 SD vs 226.7 ± 138.7 SD NG/mL), enhanced plasma levels of lipoprotein(a) (41.4 ± 38.6 SD vs 16 ± 18.2 SD mg/dL, F = 5.67, P = 0.02), high leukocyte count (9.1 ± 2.7 SD vs 6.5 ± 1.3 SD x 10 3 /μL; F = 8.42, P < 0.006), and low serum folate concentration (5.3 ± 1.8 SD vs 7.1 ± 2.7 NG/mg; F = 4.34, P = 0.04). During follow-up the prothrombin time was prolonged (F = 4.34, P = 0.04) and leukocyte count decreased (F = 7.39, P < 0.019) in the APV patients, whereas fibrinogen, D-dimer, lipoprotein(a), and folate were unchanged. CONCLUSION: Our results provide evidence suggesting an involvement of the hemostatic system in APV.

Download Full-text

Hemostatic Abnormalities and Changes Following Bone Marrow Transplantation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960401000406 ◽

2004 ◽

Vol 10 (4) ◽

pp. 341-350 ◽

Cited By ~ 15

Author(s):

Takeshi Matsumoto ◽

Hideo Wada ◽

Hiroyoshi Nishiyama ◽

Tomomi Hirano ◽

Miho Sakakura ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Plasminogen Activator ◽

Plasma Levels ◽

Marrow Transplantation ◽

Allogeneic Bone Marrow Transplantation ◽

Allogeneic Bone ◽

Survivor Group ◽

Pai 1 ◽

D Dimer

Hemostatic parameters were examined in 39 patients who underwent allogeneic bone marrow transplantation (BMT). Twenty-six patients survived and 13 patients died within 6 months after BMT. The main causes of death were acute graft-versus-host disease (GVHD: n=6), veno-occlusive disease (VOD: n=2), and thrombotic microangiopathy (TMA: n=2). Plasma levels of D-dimer and thrombomodulin (TM) were significantly elevated in the non-survivor group. Plasma levels of soluble fibrin (SF) and Fas were significantly elevated in the non-survivor group at 1 to 4 weeks after BMT. Plasma levels of thrombin-antithrombin complex (TAT), D-dimer, and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex) were significantly elevated in patients with complications after BMT. Plasma levels of TAT, D-dimer, and tPA-PAI-1 complex were significantly elevated in patients with GVHD. These results suggest that abnormalities of hemostatic parameters might predict poor outcomes or complications in patients with BMT.

Download Full-text

PENGARUH HIPERKOAGULASI TERHADAP MORTALITAS ASTROSITOMA PADA PEMANTAUAN 12 BULAN

Majalah Kedokteran Neurosains Perhimpunan Dokter Spesialis Saraf Indonesia ◽

10.52386/neurona.v37i1.96 ◽

2020 ◽

Vol 37 (1) ◽

Author(s):

Among Wibowo ◽

Tiara Aninditha ◽

Henry Riyanto Sofyan ◽

Rini Andriani

Keyword(s):

Brain Tumor ◽

Prothrombin Time ◽

Partial Thromboplastin Time ◽

High Grade Glioma ◽

Activated Partial Thromboplastin Time ◽

Hypercoagulable State ◽

Cancer Center ◽

High Grade ◽

D Dimer

EFFECT OF HYPERCOAGULABILITY TO ASTROCYTOMA MORTALITY WITHIN 12-MONTHS OF FOLLOW UPABSTRACTIntroduction: Astrocytoma is the most common primary brain tumor. Hypercoagulable state is one of brain tumor complications which can cause vein thromboembolism (VTE). Vein thromboembolism incidence is increased in astrocytoma patients. Hypercoagulable state in astrocytoma could lower patient’s survival.Aim: To investigate the effect of hypercoagulable state on mortality within 12 months of follow up in astrocytoma patients.Methods: This study design was retrospective cohort. This research data was taken from medical records in Cipto Mangunkusumo General Hospital and Dharmais Cancer Center Hospital on December 2017-February 2018. The subjects were adult astrocytoma patients who had histopathology and hemostasis examination. The variables investigated in this study were gender, age, prothrombin time (PT), activated partial thromboplastin time (aPTT), and D-dimer. Data processed descriptively and analytically using SPSS ver. 20 for Windows.Results: There were 49 subjects in this research. Around 30 (61.2%) subjects were men and 20 (40.8%) subjects aged >50 years old. High grade glioma was found in 39 (79.6%) subjects and hypercoagulable state was found in 34 (69.4%) subjects. There were 20 subjects deceased in 12-month follow-up. Subjects with hypercoagulable state had relative risk (RR) of 3.97 more susceptible to die in 12-month follow-up compared to control (p=0.009).Discussion: Hypercoagulation was a mortality risk factor in 12-month follow-up in patients with astrocytoma.Keywords: Astrocytoma, hypercoagulation, mortality within 12-months of follow upABSTRAKPendahuluan: Astrositoma merupakan tumor otak primer yang paling sering ditemukan. Salah satu komplikasi dari tumor otak adalah keadaan hiperkoagulasi. Keadaan hiperkoagulasi dapat menyebabkan tromboemboli vena. Insiden tromboemboli vena meningkat pada astrositoma. Keadaan hiperkoagulasi pada astrositoma dapat menurunkan kesintasan atau meningkatkan mortalitas pada pasien astrositoma.Tujuan: Mengetahui pengaruh hiperkoagulasi pada mortalitas pasien astrositoma dalam 12 bulan pemantauan.Metode: Penelitian kohort retrospektif terhadap pasien tumor otak jenis astrositoma yang dirawat oleh Divisi Neuroonkologi di RSUPN Dr. Cipto Mangunkusumo (RSCM) dan RS Pusat Kanker Dharmais (RSKD) pada bulan Desember 2017 hingga Februari 2018. Sumber data adalah data sekunder berupa rekam medis pasien dewasa yang telah memiliki hasil pemeriksaan histopatologis dan hemostasis. Variabel yang diambil dalam penelitian ini adalah jenis kelamin, usia, prothrombin time (PT), activated partial thromboplastin time (aPTT), dan D-dimer. Data diolah secara deskriptif dan analitik bivariat menggunakan SPSS ver. 20 for Windows.Hasil: Terdapat 49 subjek dalam penelitian ini yang mayoritas (61,2%) laki-laki, berusia <50 tahun (59,2%), dan memiliki jenis high grade gliomas (75,8%). Sebagian besar subjek mengalami hiperkoagulasi (69,4%) dan dalam kondisi hidup (59,2%) pada 12 bulan pascaperawatan. Subjek dengan hiperkoagulasi memiliki risiko relatif (RR) 3,97 kali lebih rentan mengalami kematian setelah 12 bulan dibandingkan kontrol (p=0,009).Diskusi: Hiperkoagulasi merupakan salah satu faktor risiko kematian dalam 12 bulan pada pasien astrositoma.Kata kunci: Astrositoma, hiperkoagulasi, mortalitas 12 bulan

Download Full-text

Adaptation of Coagulation and Fibrinolysis in Allogeneic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v110.11.3023.3023 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3023-3023

Author(s):

Anne Pinomaki ◽

Liisa Volin ◽

Lotta Joutsi-Korhonen ◽

Jussi Oskari Virtanen ◽

Marja Lemponen labtech ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Thrombin Generation ◽

Acute Gvhd ◽

Conditioning Therapy ◽

Pai 1 ◽

D Dimer ◽

Coagulation And Fibrinolysis

Abstract Allogeneic stem cell transplantation (SCT) seems to result in activation of coagulation and fibrinolysis. We characterised the outcome of SCT and graft versus host disease (GvHD) in association with the adaptive mechanisms of coagulation and fibrinolysis. 30 patients given myeloablative conditioning with cyclophosphamide and total body irradiation underwent allogeneic SCT for a hematological malignancy. 19 patients received the transplant from a sibling and 11 from an unrelated donor. GvHD prophylaxis consisted of cyclosporine and methotrexate, and in addition methylprednisolone in case of a sibling donor. Eight patients developed GvHD during the 3-month follow-up. Several coagulation and fibrinolysis activities were serially assessed: antithrombin, protein C (PC), FVIII, prothrombin fragments 1+2 (F1+2), D-dimer, tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1). During the conditioning therapy as an early sign of thrombin generation, F1+2 increased 3-fold and D-dimer 4-fold, compatible with enhanced fibrin turnover. The activity of tPA reached its maximum already before the engraftment and that of PAI-1 diminished accordingly. FVIII increased steadily from normal to reach maximum (up to 273% ±104%, median ±SD, p<0.001) after engraftment. Interestingly, the natural anticoagulant, PC rose (up to 189% ± 63%) in parallel with FVIII, but showed a 5-fold individual variability. After the engraftment the FVIII, PC and antihrombin levels were highly interrelated. Clinically relevant prognostic association was observed between early low PC activity and the appearance of GvHD: the level of PC lower than 90% during the conditioning therapy was associated and even predicted (p=0.007) acute GvHD (OR=16.7). After the transplantation the level of F1+2 over 2.5 nmol/l associated and predicted the non-relapse mortality (p=0.024). Three patients with the largest early thrombin generation all died during a longer follow-up (6–24 months). Also, elevated PAI-1 activity (>10 U/ml) predicted the non-relapse mortality (p=0.013). In conclusion, early activation of coagulation and fibrinolysis is followed by increased FVIII and PC activities in SCT. Early marked thrombin generation and elevated PAI-1 associated with the non-relapse mortality and low PC activity with the appearance of acute GvHD.

Download Full-text