DRUGS AFFECTING THE BLOOD: COAGULANTS AND ANTI-COAGULANTS
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Drugs affecting the blood are primarily divided into
- anticlotting drugs and
- drugs that facilitate clotting.
Anticlotting drugs are divided into
- anticoagulants (warfarin, heparins, vitamin K antagonists)--disrupt the creation of clots by interfering at points within the clotting cascade;
- antiplatelet agents (aspirin)--inhibit platelet aggregation (platelets can't stick together and form clots); and
- thrombolytics (t-PA)--class of drug that dissolves clots.
- Vitamin K: Vitamin K is required in the clotting cascade, so individuals with vitamin K deficiencies (long time alcoholics) can be given Vitamin K supplementation orally or by injection. Other Vitamin K deficiency is seen in neonates and those with hepatobiliary or pancreatic disease.
- Blood Products, typically available in fresh frozen plasma (FFP), which contain clotting factors: blood products like fresh frozen plasma (FFP) and clotting factors are given intravenously to patients who have inherited bleeding disorders like hemophilia or who are experiencing DIC (disseminated intravascular coagulopathy) [SEE BELOW].
- Antifibrinolytic Drugs: slow down the absorption of clots in order to reduce bleeding after surgery or during menstrual bleeding.
Phases of the Hemostatic Process
1) ENDOTHELIAL INJURY AND FORMATION OF THE PLATELET PLUG.
Adhesion – The deposition of platelets on the subendothelial matrix
Aggregation – Platelet-platelet cohesion
Secretion – The release of platelet granule proteins
Procoagulant activity – The enhancement of thrombin generation
Propagation of the clotting process by the coagulation cascade.
The central feature of the clotting cascade is the sequential activation of a series of proenzymes or precursor proteins into active enzymes, resulting in significant stepwise response amplification.
- The EXTRINSIC (Common) Pathway:
Extrinsic TF and Intrinsic Factor XII --> Factor X
Generation or exposure of tissue factor (TF) at the wound site, its interaction with factor VIIa and the subsequent generation of activated factor X, are the primary physiologic events in initiating clotting; meanwhile...
- The INTRINSIC Pathway components (i.e., factors VIII, IX, XI) are responsible for the amplification of this process.
Both pathways converge on the activation of factor X which, as a component of prothrombinase, converts prothrombin to thrombin, the final enzyme of the clotting cascade. Thrombin converts fibrinogen from a soluble plasma protein into an insoluble fibrin clot:
→ (prothrombin--> thrombin) → (fibrinogen → fibrin)
(As an example, in the EXTRINSIC Clotting Pathway, the generation of a small number of factor VIIa molecules will activate many molecules of factor X, which in turn generates even larger numbers of thrombin molecules, which in the INTRINSIC Clotting Pathway converts fibrinogen to fibrin to enmesh and reinforce the platelet plug.)
2) TERMINATION OF CLOTTING BY ANTI-THROMBOTIC CONTROL MECHANISMS.
3) REMOVAL OF THE CLOT BY FIBRINOLYSIS.
Medications Affecting Clotting
DRUGS ENHANCING CLOTTING:
- Anticoagulant reversal agents
- Heparin antagonists
- Platelet-stimulating agents
DRUGS INTERFERING WITH CLOTTING (ANTICOAGULANTS):
- coumarins and indandiones
- factor Xa inhibitors
- thrombin inhibitorS
- Platelet inhibitors
Clots Gone Wild: DIC
DISSEMINATED INTRAVASCULAR COAGULOPATHY (DIC):
It seems counter-intuitive, but hemorrhage from DIC is a case of too much clotting. When all of the clotting factors are consumed in this over-clotting situation, hemorrhage is unchecked. Such "consumptive coagulopathy," as well as toxicities that can interfere with clotting, can give similar presentations.
Causes of DIC include:
- Infection and sepsis,
- malignancy (leukemia and tumors),
- trauma (especially head trauma),
- obstetrical complications,
- transfusion reactions,
- heat stroke,
- intravascular hemolysis (malaria),
- crush injuries,
- amphetamine overdose,
- snakebite (rattlesnake, viper),
- hereditary deficiencies, and
- transplant rejection.
Treatment for DIC--again, counter-intuitively--is with heparin to interfere with clotting (even though the patient is hemorrhaging!). This is an ICU-level catastrophe with a high mortality rate.
In the Field
Signs and Symptoms of Clotting Disorders
In the field, the most important finding toward suspicion of a clotting disorder is seeing petechiae or ecchymoses. You will not have what is necessary to treat DIC and so the sooner you transport the patient for heparin therapy and transfusions of clotting factors, the better the chance of the patient's survival.