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Media Gallery

Coagulation Cascade
Obituary in the Salem Gazette (Massachusetts) of a 19-year-old man, March 22, 1796.
The hemostatic pathway: role of factor IX.
Activation of factor IX and function of the intrinsic tenase complex. Activation of factor IX is followed by formation of the intrinsic tenase complex, which activates factor X to activated factor X, leading to a second and larger burst of thrombin production during activation of hemostasis.
Vitamin K–dependent carboxylation of precursor factor IX to procoagulant factor IX. Carboxylation of glutamate (Glu) to gamma-carboxyglutamate (Gla) residues in the precursor protein of the vitamin K–dependent factors occurs in the endoplasmic reticulum of the hepatocyte. Reduced vitamin K is oxidized in this process. Warfarin prevents the reduction and recycling of oxidized vitamin K.
Cell surfaced-directed hemostasis. Initially, a small amount of thrombin is generated on the surface of the tissue factor (TF)–bearing cell. Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation. (Adapted from Hoffman and Monroe, Thromb Haemost 2001, 85(6): 958-65.)
Knee radiographs in a patient with advanced hemophilic arthropathy demonstrate chronic severe arthritis, fusion, and loss of cartilage and joint space.

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Table 1. Severity, Factor Activity, and Hemorrhage Type

Classification	Factor Activity, %	Cause of Hemorrhage
Mild	>5-40	Major trauma or surgery
Moderate	1-5	Minor trauma or surgery; occasional spontaneous hemarthrosis
Severe	< 1	Lifelong spontaneous hemorrhages and hemarthroses starting in infancy

Table 2. General Guidelines for Factor Replacement for the Treatment of Bleeding in Hemophilia B

Indication or Site of Bleeding	Factor level Desired, %	FIX Dose, IU/kg^*	Comment
Severe epistaxis; mouth, lip, tongue, or dental work	20-50	20-50	Consider aminocaproic acid (Amicar), 1-2 d
Joint (hip or groin)	40	40	Repeat transfusion in 24-48 h
Soft tissue or muscle	20-40	40	No therapy if site small and not enlarging (transfuse if enlarging)
Muscle (calf and forearm)	30-40	40	None
Muscle deep (thigh, hip, iliopsoas)	40-60	40-60	Transfuse, repeat at 24 h, then as needed
Neck or throat	50-80	50-80	None
Hematuria	40	40	Transfuse to 40% then rest and hydration
Laceration	40	40	Transfuse until wound healed
GI or retroperitoneal bleeding	60-80	60-80	None
Head trauma (no evidence of CNS bleeding)	50	50	None
Head trauma (probable or definite CNS bleeding, eg, headache, vomiting, neurologic signs)	100	100	Maintain peak and trough factor levels at 100% and 50% for 14 d if CNS bleeding documented^†
Trauma with bleeding, surgery	80-100	100	10-14 d

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Author

Robert A Zaiden, MD Adjunct Associate Professor, Division of Cancer Medicine, Baptist MD Anderson Cancer Center

Robert A Zaiden, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Srikanth Nagalla, MD, MS, FACP Chief of Benign Hematology, Miami Cancer Institute, Baptist Health South Florida; Clinical Professor of Medicine, Florida International University, Herbert Wertheim College of Medicine

Srikanth Nagalla, MD, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion; Alnylam; Kedrion; Sanofi; Dova; Apellis; Pharmacosmos<br/>Serve(d) as a speaker or a member of a speakers bureau for: Sobi; Sanofi; Rigel.

Acknowledgements

Dimitrios P Agaliotis, MD, PhD, FACP Consulting Staff, Department of Medicine, Baptist Health System