ISSN: 1300-7777 E-ISSN: 1308-5263
The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin [Turk J Hematol]
Turk J Hematol. 2016; 33(2): 112-118 | DOI: 10.4274/tjh.2014.0312  

The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin

Hadil A Al Otair1, Abdel Galil M Abdel Gader2, Syed M Khurshid1, Abdulaziz H. Alzeer1, Abdulkareem Almomen3, Mashael Alshaikh4, Farja Al Gahtani3, Zohair A. Alaseri5, Hossam A.H.abdelrazik5
1King Saud University College of Medicine, King Khalid University Hospital, Department of Critical Care, Riyadh, Saudi Arabia
2King Saud University College of Medicine, King Khalid University Hospital, Department of Physiology, Riyadh, Saudi Arabia
3King Saud University College of Medicine, King Khalid University Hospital, Department of Medicine, Riyadh, Saudi Arabia
4King Saud University College of Medicine, King Khalid University Hospital, Department of Pharmacy, Riyadh, Saudi Arabia
5King Saud University College of Medicine, King Khalid University Hospital, Department of Emergency, Riyadh, Saudi Arabia

INTRODUCTION: Sepsis syndrome is usually accompanied by activation of blood coagulation mechanisms. Earlier studies found deficiencies of the 3 main natural anticoagulants, antithrombin, protein C, and protein S. However, none of these inhibitors block tissue factor, the prime trigger of coagulation during sepsis that is controlled specifically by the tissue factor pathway inhibitor (TFPI). The aim of this study was to characterize the fluctuations in the levels of natural anticoagulants, particularly TFPI, in the course of sepsis and to find out their association with the anticoagulant action of the lowmolecular- weight heparin enoxaparin.
METHODS: We studied 51 consecutive patients with sepsis. Blood samples were collected from patients at baseline (0 h) and at 4, 12, and 24 h after enoxaparin administration. The following assays were undertaken using commercial kits: activated partial thromboplastin time, prothrombin time, thrombin time, total and free TFPI, protein C and protein S, antithrombin, fibrinogen, and anti-factor Xa.
RESULTS: Before enoxaparin administration, there was significant prolongation of the prothrombin time and activated partial thromboplastin time, and this remained the case in the 3 subsequent samples. There was marked reduction in the levels of antithrombin, protein C, and total and free protein S to below control values throughout the study. In contrast, plasma levels of both total and free TFPI were markedly elevated and increased after enoxaparin therapy. Anti-factor Xa levels were within the therapeutic range throughout. There was no difference in TFPI levels between those patients who died and those who survived.
DISCUSSION AND CONCLUSION: Sepsis triggered marked release of TFPI from endothelial cells. This persisted and was increased further following the administration of enoxaparin. In contrast, there was marked consumption of the natural coagulation inhibitors antithrombin, protein C, and protein S. These results go some way towards explaining why the therapeutic use of recombinant TFPI fails to correct sepsisassociated coagulopathy.

Keywords: Coagulation, Sepsis, Enoxaparin


Profilaktik Enoksaparin Alan Sepsis Hastalarında Doku Faktör Yolak İnhibitörü Düzeyleri

Hadil A Al Otair1, Abdel Galil M Abdel Gader2, Syed M Khurshid1, Abdulaziz H. Alzeer1, Abdulkareem Almomen3, Mashael Alshaikh4, Farja Al Gahtani3, Zohair A. Alaseri5, Hossam A.H.abdelrazik5
1King Saud University College of Medicine, King Khalid University Hospital, Department of Critical Care, Riyadh, Saudi Arabia
2King Saud University College of Medicine, King Khalid University Hospital, Department of Physiology, Riyadh, Saudi Arabia
3King Saud University College of Medicine, King Khalid University Hospital, Department of Medicine, Riyadh, Saudi Arabia
4King Saud University College of Medicine, King Khalid University Hospital, Department of Pharmacy, Riyadh, Saudi Arabia
5King Saud University College of Medicine, King Khalid University Hospital, Department of Emergency, Riyadh, Saudi Arabia

GİRİŞ ve AMAÇ: Sepsis sendromuna genellikle kan pıhtılaşma sisteminin aktivasyonu eşlik eder. İlk çalışmalar ana doğal 3 antikoagülan olan antitrombin, protein C ve protein S eksikliği bulmuştur. Bununla birlikte, bu inhibitörlerin hiç biri doku faktörü bloke etmez, sepsis sırasındaki koagülasyon tetiklenişi özelllikle doku faktör yolak inhibitörü (DFYİ) ile kontrol edilir. Bu çalışmanın amacı sepsis sırasındaki doğal antikoagülan ve özellikle DFYİ düzeyi dalgalanmalarını karakterize etmek ve bunların düşük moleküler ağırlıklı heaprin enoksaparinin antikoagülan eylemi ile ilişkilerini öğrenmekti.
YÖNTEM ve GEREÇLER: Ardışık 51 sepsis hastası çalışmaya alındı. Taban (0 saat) ve enoksaparin verimesinden 4, 12, 24 saat sonra kan örnekleri alındı. Aşağıdaki deneyler ticari kitleri kullanılarak yapılmıştır; parsiyel tromboplastin zamanı, protrombin zamanı, trombin zamanı, toplam ve serbest DFYİ, protein C ve protein S, antitrombin, fibrinojen, ve aktif anti-faktör Xa.
BULGULAR: Enoksaparin uygulamadan önce ptorombin zamanı ve aktif parsiyel protrombin zamanında önemli uzama vardı. Bu durum sonraki 3 örneklemde de devam etti. Çalışma boyunca antitrombin, protein C, toplam ve serbest protein S seviyeleri değerlerinde kontrollere göre belirgin bir azalma oldu. Buna karşılık, hem toplam hem de serbest plazma DFYİ değerleri belirgin biçimde yükseldi ve enoksaparin tedavisinden sonra arttı. Anti faktör Xa düzeyleri terapötik aralık içindeydi. Vefat eden ve sağ kalan hastalar arasında DFYİ düzeyi açısından fark yoktu.
TARTIŞMA ve SONUÇ: Sepsis, endotel hücrelerinden belirgin DFYİ salınımı ile tetiklenir. Bu, enoksaparin uygulmasını takiben kalıcı olmuş ve daha da artmıştır. Bunun aksine, doğal koagülasyon inhibitörleri antitrombin, protein C ve protein S’nin belirgin tüketimi vardı. Bu sonuçlar, tedavi amaçlı rekombinant DFYİ kullanımının sepsis ilişkili koagülopatiyi düzeltmek için neden başarısız olduğunu doğru biçimde açıklamaktadır.

Anahtar Kelimeler: Koagülasyon, Sepsis, Enoksaparin


Hadil A Al Otair, Abdel Galil M Abdel Gader, Syed M Khurshid, Abdulaziz H. Alzeer, Abdulkareem Almomen, Mashael Alshaikh, Farja Al Gahtani, Zohair A. Alaseri, Hossam A.H.abdelrazik. The Levels of Tissue Factor Pathway Inhibitor in Sepsis Patients Receiving Prophylactic Enoxaparin. Turk J Hematol. 2016; 33(2): 112-118

Corresponding Author: Hadil A Al Otair, Saudi Arabia


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