THree most common preparation of heparin
- Unfractionated Heparin
- Low molecular weight heparin
- Fondaparinux
Unfractionated Heparin is administered
Intravenously it can’t be given orally because the proteins will denature in the stomach acid
What is the relationship between UFH dose and response?
It is tricky and thus needs to be monitored with an aPTT
APTT
Activated Partial Thromboplastin Time
What is normal APTT….What is Therapuetic APTT?
Normal 25-36 seconds, Therapy with UFH typically prolongs that 2-2.5 times that of the normal value
Anticoagulants
Substances that prevent the synthesis of a fibrin network which inhibits coagulation and the formation of thrombi
Thrombolytics/Fibrinolytics
Substances that promote the destruction of already formed blood clots or thrombi by disrupting the fibrin mesh
Antiplatelets
Drugs that reduce the adhesion and aggregation of platelets
Antifibrinolytics
Drugs that promote the formation of clots and prevent excessive bleeding
Anticoagulant divisions
- Indirect thrombin inhibitors (heparin)
- Coumarin Anticoagulants (Warfarin)
- Direct Thrombin Inhibitors
- Direct Active Factor X (Xa) Inhibitors
UFH is contraindicated in patients who are/have
- hypersensitive to the drug
- actively bleeding
- hemophilia
- significant thrombocytopenia
How is UFH in pregnancy?
Generally safe but LMWH are considered safer
UFH overdose
Treated with IV protamine sulfate
How many platelets can a megakaryocyte produce.
3000….about
20 -30% of platelets are stored where?
Spleen
Platelet life span
5-20 days
Phases of Hemostasis
- Vascular Spasm
- Platelet plug formation
- Blood clotting
Vasospasm is stimulated by?
The injury itself and the SNS
Platelet plug formation
Platelets stick to exposed collagen, swell, and spiked processes
Platelet plugs are effective in preventing loss due to small injuries
GPIa receptors
Glycoprotein receptors on platelets that are used to adhere to exposed collagen, or endothelium
Von Willebrands Factor
A protein found in blood plasma, platelets and walls of blood vessels and using GPIb receptors it specifically causes platelets to attach firmly and spread across a damaged endothelial surface.
Platelets undergo many structural deformations in adhesion and adhesion stimulates the release of what factors from platelets
- ADP
- Thromboxane A2 (TA2, TXA2; (a prostaglandin)
- Serotonin (5-HT)
What do ADP, TXA and 5-HT do?
They attach to receptors on other platelets making them more sticky and likely to aggregate
GPIIb/IIIa receptor
It is the receptor on platelets that fibrinogen and other macromolecules bind to
Factor I
Fibrinogen
Factor II
Prothrombin
Factor III
Thromboplastin
Factor IV
Calcium
Factor V
Proaccelerin (labile factor)
Factor VII
Proconvertin
Factor VIII
Antihemophilic factor A
Factor IX
Antihemophilic factor B
Plasma thromboplastin component
Christmas factor
Factor X
Stuart Prower factor
Factor XI
Plasma thromboplastin antecedent
Hemophilia C
Rosenthal Syndrome
Factor XII
Hageman factor
Factor XIII
Fibrin stabilizing factor
Lake-Loran’s factor
Which are the vitamin K dependent clotting factors?
II, VII, IX, X
Natural anticoagulants
Thrombi Mosul in
Antithrombin III
Heparin Cofactor II
Thrombomodulin
Found on endothelial cells it combines with thrombin to e protein c and protein s degrade factors V and VIII
antithrombin III
glycoprotein produced by liver inhibits factor x and thrombin
Heparin cofactor II
Plasma protein made in liver and inhibits thrombin
Fibrinolysis inhibitors
Plasminogen activator inhibitor 1
Plasminogen activator inhibitor 2
Alpha 2 -antiplasmin
Alpha 2 macroglobulin
Petechia
Pinpoint hemorrhage on the forearm
Coagulation tests
Determine the functions of the intrinsic and extrinsic components of the coagulation system
Prothrombin time
Assess the extrinsic pathway
International normalized ration INR
Way to compare prothrombin time
INR is used most often to….?
Monitor the effectiveness of s such as warfarin (coumadin)
What does APTT test
Assesses the intrinsic pathway, after Ca is added then kaolin and phospholipids are added to substitute for contact factor
APTT is most used to test?
Used to monitor Heparin therapy
Thrombin clotting Time
Assesses the common pathway, ultimately assessing the conversion of fibrinogen to fibrin
Coagulation factor assays
Determine actually deficiencies of specific clotting factors
Hemophilia A
Factor VIII deficiency
X linked disorder
Prolongation of APTT; PT normal
Hemophilia B
Christmas Disease
X linked
Factor IX deficiency
Prolongation of APTT; PT normal
Most serious sites of hemophilia bleeding
Joint capsule
Skeletal muscles
GI tract
Brain
Hemophilia treatment
Factor IV replacement, apart from routine supplementation, extra factor replacement is given after surgical procedures or trauma
Von Willedbrand’s factor has 2 major roles
Mediating platelet adhesion
Stabilizing factor VIII
Von Willebrands Disease
Most common inherited bleeding disorder affects men and women
Has prolonged APTT and PT