Page 636 - Basic _ Clinical Pharmacology ( PDFDrive )

622 SECTION VI Drugs Used to Treat Diseases of the Blood, Inflammation, & Gout

TABLE 34–3 Therapeutic products for the treatment of coagulation disorders. 1

Half-Life of
Factor Deficiency State Hemostatic Levels Infused Factor Replacement Source
I Hypofibrinogenemia 1 g/dL 4 days Cryoprecipitate, FFP
II Prothrombin deficiency 30–40% 3 days Prothrombin complex concentrates (intermediate purity factor
IX concentrates)
V Factor V deficiency 20% 1 day FFP
VII Factor VII deficiency 30% 4–6 hours FFP
Prothrombin complex concentrates (intermediate purity factor
IX concentrates) Recombinant factor VIIa
VIII Hemophilia A 30–50% 12 hours Recombinant factor VIII products
100% for major Plasma-derived high purity concentrates
bleeding or trauma 2
Cryoprecipitate
Some patients with mild deficiency will respond to DDAVP
IX Hemophilia B 30–50% 24 hours Recombinant factor IX products
Christmas disease 100% for major Plasma-derived high purity concentrates
bleeding or trauma
X Stuart-Prower defect 25% 36 hours FFP
Prothrombin complex concentrates
XI Hemophilia C 30–50% 3 days FFP
XII Hageman defect Not required Treatment not necessary
von von Willebrand disease 30% Approximately Intermediate purity factor VIII concentrates that contain
Willebrand 10 hours von Willebrand factor
Type I patients respond to DDAVP
Cryoprecipitate 2
XIII Factor XIII deficiency 5% 6 days FFP
Cryoprecipitate
FFP, fresh frozen plasma; DDAVP, 1-deamino-8-d-arginine vasopressin.
1
For warfarin overdose or coumarin rodenticide poisoning, a four-factor concentrate (II, VII, IX, X) is available. Antithrombin concentrates are available for patients with thrombosis
in the setting of antithrombin deficiency. Activated protein C concentrates were approved for treatment of sepsis but withdrawn from the market in 2011 following publication
of a study demonstrating no benefit in sepsis and increased bleeding risk.
2 Cryoprecipitate should be used to treat bleeding in the setting of factor VIII deficiency and von Willebrand disease only in an emergency in which pathogen-inactivated products
are not available.

dosing in the case of Idelvion. Intermediate purity factor VIII con- Desmopressin acetate increases the factor VIII activity of
centrates (as opposed to recombinant or high purity concentrates) patients with mild hemophilia A or von Willebrand disease. It can
contain significant amounts of von Willebrand factor. Humate-P be used in preparation for minor surgery such as tooth extraction
is a factor VIII concentrate that is approved by the FDA for the without any requirement for infusion of clotting factors if the
treatment of bleeding associated with von Willebrand disease. patient has a documented adequate response. High-dose intrana-
Vonicog alfa is a recombinant von Willebrand factor product sal desmopressin (see Chapter 17) is available and has been shown
approved for treatment and control of bleeding in adults with von to be efficacious and well tolerated by patients.
Willebrand disease. Fresh frozen plasma is used for factor deficien- Freeze-dried concentrates of plasma containing prothrombin,
cies for which no recombinant form of the protein is available. A factors IX and X, and varied amounts of factor VII (Proplex,
four-factor plasma replacement preparation containing vitamin etc) are commercially available for treating deficiencies of these
K–dependent factors II VII, IX, and X (4F PCC, Kcentra) is avail- factors (Table 34–3). Each unit of factor IX per kilogram of
able for rapid reversal of warfarin in bleeding patients. body weight raises its activity in plasma 1.5%. Heparin is often
added to inhibit coagulation factors activated by the manufactur-
Clinical Uses ing process. However, addition of heparin does not eliminate all
thromboembolic risk.
Hemophilia A and B patients are given factor VIII and IX replace- Some preparations of factor IX concentrate contain activated
ment, respectively, as prophylaxis to prevent bleeding, and in clotting factors, which has led to their use in treating patients
higher doses to treat bleeding events or to prepare for surgery. with inhibitors or antibodies to factor VIII or factor IX.