Hemorrhage

Liang A

Disseminated Intravascular Coagulation (DIC)

Clinical Cases Applicability: Postpartum hemorrhage, HELLP Syndrome, Placental abruption, Fetal demise, Amniotic fluid embolism

Learning Objectives:

1) Understand the basic principles of normal hemostasis

2) Understand which clotting factors are measured in commonly ordered coagulation labs 3) Understand the pathophysiology of DIC

Clinical Presentation: Bleeding, hypotension out of proportion to bleeding, and coagulopathy

How does a clot form? (See figure 1)

Tissue factor at the wound site + VIIa  activates X and IX to generate small amounts of thrombin  activates factors V, VIII, XI and platelets, which leads to amplification of thrombin How does a clot stop forming?

1)Antithrombin inhibits thrombin 2)Activated protein C block activation of factors V and VIII 3)Tissue factor pathway inhibitor blocks activation of factor VII

How is a clot removed (fibrinolytic system)?

Fibrin & tissue plasminogen activator bind plasminogen  plasmin  cleaves fibrin  releases FDP (fibrin degradation products)

What clotting factors are measured when you order aPTT? PT?

-aPTT: “Intrinsic” pathway; all coagulation factors except VII and tissue factor

-PT: “Extrinsic” pathway; tissue factor, VII, V, X, II (prothrombin), fibrinogen

-factor VII, IX, X, II, protein C&S are vitamin K dependent  altered by warfarin

What happens in DIC? See figure 2

Coagulation and fibrinolysis become abnormally activated within the vasculature

Endothelial damage  activation of coagulation cascade  extensive thrombi in microvasculature and larger vesselsconsumption of factors, platelets and anticoagulant factors (S, C, antithrombin) consumption greater than production “consumptive coagulopathy”fibrinolysislarge amount of FDP interferes with fibrin clot formation and platelet aggregationtissue/organ damage from reduced perfusion, thrombosis and/or bleeding

Pathophysiology in pregnancy:

Decidual cells lining the vascular bed of the placenta strongly express tissue factor (similar to endothelial cells);

TF released at sites of decidual traumacoagulation cascade activation

-Abruption, fetal demise: Release of procoagulants due to significant injury/necrosis of fetoplacental tissue

-AFE: Amniotic fluid rich in procoagulants and anticoagulants

-Preeclampsia, HELLP: Contribute to endothelial cell damage

-Hemorrhage leading to shock: severe tissue hypoxia proposed to result in release of TF from damaged cells

What are laboratory findings that are consistent with DIC?

↓Platelets, hemolytic changes in peripheral blood smear (anemia & schistocytes), ↓fibrinogen (normal fibrinogen levels range from 373 -619 mg/dL in 3rd trimester), ↑D-dimer (FDP), and ↑ PT and aPTT.

How do you treat DIC?

Focused on correcting the underlying cause, maintenance of maternal volume status, and replacement of blood products: platelets, fresh frozen plasma (contains all coagulation factors), cryoprecipitate (smaller volume than FFP, rich in von Willebrand factor, VIII, XIII, fibrinogen) Liang A

Figure 2

Tissue factor +VIIa

Xa

IXa

VIIIa

Va

IIa

(

Thrombin

)

XIa

XIIa

Fibrinogen

Fibrin

Plasmin

Plasminogen

TPA

TF pathway inhibitor

Protein C

Activated

Protein C

Protein S

PTT (intrinsic)

PT (Extrinsic)

Disseminated Intravascular Coagulation (DIC)

Figure 1

• Gabbe, Steven G. Obstetrics: Normal And Problem Pregnancies. Seventh edition. Philadelphia, PA: Elsevier, 2017.

• Leung, LLK. Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in adults. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (2016)

• Leung, LLK. Overview of hemostasis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (2016)

• Ramin, SM. Disseminated intravascular coagulation during pregnancy. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (2016)