Journal Presentation

Dr. Ummeh Habiba Islam (Punam)

Resident (Phase A)

Department of Hematology

Bangabandhu Sheikh Mujib Medical University

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Disseminated intravascular coagulation: epdemiology, biomarkers, and management�

Kasper Adelborg, Julie B. Larsen, Anne‐Mette Hvas

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British Journal of Haematology (BJH)

Volume: 192, Issue 5, Page: 803-818

Published on 8^th February 2021

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Introduction

• Disseminated intravascular coagulation (DIC) is a systemic activation of the coagulation system.

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• Infections, cancer, obstetrical complications are some of important responsible factors for propagation of DIC.

Introduction: Definition

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DIC is an acquired syndrome characterized by the intravascular activation of coagulation with a loss of localization arising from different causes.

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Introduction: Aetiology

• Malignancies
• Obstetrical complications
• Trauma (Head trauma)
• Secondary to vascular trauma
• Kasabach-Merritt syndrome
• Aortic aneurisms

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Introduction: Clinical presentation

Highly variable

• Depends on dynamic balance between
1. Clot formation in the microvasculature
2. Degree of consumption of coagulation factors, inhibitors & platelets

Introduction: Clinical Presentation (Cont’d)

Based on severity & stage DIC is categorized as

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1. Non-overt (Early)

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• Overt (Decompensated)

Introduction: Clinical Presentation (Cont’d)

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• Acute
• Chronic
• May be subclinical

Introduction: Clinical Presentation (Cont’d)

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• Bleeding & Thrombosis
• Dermatological bleeding (Petechiae & Ecchymosis)
• GI bleeding
• Urogenital bleeding
• Bleeding in vicinity of surgical sites and/or serous cavity

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• Organ failure (When clot formation primarily involves microvasculature)

Epidemiology

• The occurrence of DIC is not directly comparable between studies.

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• In one study in Japan, DIC occurred in 1286 (that is 1%) of 123 231 patients hospitalized & the number is around 10–30% in the intensive-care unit (ICU) setting.

Epidemiology (Cont’d)

• 30-60% patient of sepsis & 10% solid tumor patient developed DIC.
• DIC is also observed in a significant number of patients with haematological cancers, most often in acute leukaemia, particularly acute promyelocytic leukaemia.

Epidemiology (Cont’d)

DIC is frequently seen in patients with

• Cardiac arrest survivor (~10–30%)
• Head trauma (~30–40%)

Epidemiology (Cont’d)

In pregnancy, prevalence of DIC is markedly increases

• Placental abruption
• Amniotic fluid embolism

Prevalence of DIC

Prevalence of DIC

Pathophysiology

Pathological Pathways in DIC

Pathophysiology (Cont’d)

Pathophysiology of DIC mainly done by following 4 mechanisms:

a) Increased tissue factor activity and thrombin generation is inherent to DIC

b) Platelets

c) Loss of regulation: endothelial disruption and decreased anticoagulant activity

d) Altered fibrinolysis

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Pathophysiology (Cont’d)

Increased tissue factor activity and thrombin generation

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• TF is expressed on
• monocytes in sepsis-related DIC
• malignant cells or circulating tumour-derived microparticles in cancer-related DIC.

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• In obstetric DIC, placental abruption and amniotic fluid embolism expose the circulating blood to TF.

Pathophysiology (Cont’d)

• Activation of coagulation factor VII and FX, increased TF activity leads to thrombin generation.

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• Thrombin induces platelet activation, amplification of the coagulation cascade, and fibrin formation.

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• DIC progresses, and consumption of coagulation factors and platelets leads to hypo-coagulability.

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Pathophysiology (Cont’d)

Platelets:

• Increased platelet activation in DIC occurs through
• interaction with activated endothelium and
• the direct action of thrombin on platelets.

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• In sepsis-related DIC, inflammatory cells, cytokines and pathogens interact directly with platelets and contribute to their activation

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• Cross-talk between tumour cells and platelets induces platelet activation in various cancer types.

Pathophysiology (Cont’d)

Platelet aggregation in the microcirculation leads to microthrombus formation

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Loss of regulation:

endothelial disruption and decreased anticoagulant activity

Pathophysiology (Cont’d)

Altered fibrinolysis

• Both tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) are released from the activated endothelium.

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• Decreased production and increased consumption of plasminogen, as well as increased thrombin-activatable fibrinolysis inhibitor (TAFI)

Pathophysiology (Cont’d)

• Hyper-fibrinolysis has also been described among patients with solid tumours, e.g. prostate cancer.

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• In trauma patients, dynamic changes in fibrinolysis also occur.

Current Diagnostics

The tests to diagnose DIC include:

• Platelet count
• Activated partial thromboplastin time (aPTT)
• Prothrombin time (PT)
• Fibrinogen
• Fibrin breakdown products
• Antithrombin activity

DD of DIC

Biomarkers of DIC

Treatment of DIC

The main principle of DIC treatment is management of the underlying cause.

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Treatment of DIC (Cont’d)

Treatment of DIC (Cont’d)

Antibiotic treatment

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Antibiotic treatment with ongoing adjustment according to microbial cultivation.

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Drainage of the infection focus is needed as well as surgical resection of avital tissue. �

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Treatment of DIC (Cont’d)

Supportive treatment of bleeding complications

Platelet concentrate

• Administration of platelet concentrates is recommended with a threshold at 50 * 10⁹/L in DIC patients with major bleeding or patient at high risk of bleeding

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• In obstetric DIC complicated by postpartum haemorrhage, it is especially important that the level is maintained above 50 ×10⁹/L.

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• In DIC patients with minor or no bleeding, and also in cancer patients, a threshold of 20 × 10⁹/l is accepted.

Treatment of DIC (Cont’d)

Coagulation factors

According to expert consensus, substitution by coagulation factors is indicated in patients with major bleeding and aPTT and/or PT more than 1.5 times the normal value.

• First choice fresh frozen plasma
• Vitamin K
• Fibrinogen concentrate or as cryoprecipitate.

Treatment of DIC (Cont’d)

Anti-fibrinolytics

Suppression of endogenous fibrinolysis is the most common alteration of fibrinolysis in sepsis-induced DIC.

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So, it should be reserved to patients with therapy-resistant bleeding with a clear picture of hyperfibrinolysis.

Treatment of DIC (Cont’d)

Tranexamic Acid

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The use of tranexamic acid in postpartum haemorrhage is fully established.

Treatment of DIC (Cont’d)

Anticoagulant treatment of microthrombi or overt thromboembolism:

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• The purpose of anticoagulant treatment is to restore organ�perfusion
• Unfractionated heparin and low-molecular-weight heparin

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• Low-molecular-weight heparin (LMWH)

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Treatment of DIC (Cont’d)

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• In patients with concomitant bleeding, a vena cava filter should be considered in parallel to transfusion.

Treatment of DIC (Cont’d)

Other anticoagulation drugs

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• The anti-Xa agent fondaparinux has not been evaluated in DIC patients

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• The efficacy and safety of direct oral anticoagulants in the management of DIC are currently unclear

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• Antithrombin substitution could be beneficial in DIC patients.

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Conclusion

• DIC remains difficult to diagnose early in its course prior to the development of organ failure, universal formation of microthrombi, and bleedings.

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• Using scoring systems may help in diagnosis

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• Outcome of DIC remains dismal�

Conclusion (Cont’d)

• Timely & accurate diagnosis of DIC and its underlying cause is essential for prognosis.

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• Treatment should be focused on underlying cause

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• Supportive treatment should be individualized according to underlying aetiology, symptoms & laboratory records.

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