drugs used in hemorrhagic disease Flashcards
what is hemostasis?
- hemostasis (blood stop): sequence of responses that results in wound repair
- balanced homeostasis: helps maintain circulatroy homeostasis:
- prevent prolonged hemorrhage (bleeding)
- prevent spontaneous thrombosis (clotting)
what are the stages of homeostasis?
if we have a cut and we have bleeding then…
1. vascular spasm causes vasoconstriction
2. breach of the blood vessels exposed collagen fibers causes platelets to stick, forming a plug
3. coagulation: fibrin is formed, trapping the platelets and some RBCs, forming a clot
4. clot dissolves once tissue damage is repaired
describe the first stage of homeostasis
- vasospasm (vasoconstriction)
- damaged endothelial cells (b/w blood and bv) release endothelin that signals to surrounding smooth muscle to contract
- if the smooth muscle is damaged, this will intrinsically contract as well
- immediate; restricts blood flow
describe the second stage of homeostasis
- platelet response: formation of platelet plug
- platelet adhesion: von Wilebrand’s factor (VWF) is now exposed and binds to platelets
- “stuck” platelets (platelet plug) now secrete ADP, thromboxane A (TXA2), and serotonin to:
* recruit other platelets to the site
* further promote vasoconstriction
* initiate the coagulation cascade
describe the third stage of homeostasis
- coagulation cascade
- the platelet plus is strengthened by an insoluble mesh of protein called fibrin, which together with the platelet plug form a blood clot
- fibrin is converted from fibrinogen through a series of enzymatic activation of blood factors
- conversion may occur through:
* intrinsic pathway (damaged vessel wall) - disease
* extrinsic pathway (extravascular damage) - coagulation to your arm
intrinsic vs extrinsic pathway
describe the third stage of homeostasis the intrinsic pathway
- coagulation cascade
intrinsic pathway:
- most blood coagulation factors (proteins) are produced in the liver, and are inactive within circulation
- damage to the endotheial cells reveals collagen, which activates Factor XII
- Factor XII activates Factor XI
- Factor XIa activates Factor IX
- Factor IXa, with VIIIa, activates Factor X
describe the third stage of homeostasis the extrinsic pathway
- coagulation cascade
extrinsic pathway:
- damaged extravascular cells release tissue factor (TF) into the bloodstream
- TF activates Factor VII (7)
- TF-Factor VIIa activates Factor X (10)
- expedited pathway that leads to the activation of the factor needed to produce fibrin
describe the third stage of homeostasis the common pathway
- coagulation cascade
common pathway:
- Factor X is needed to convert prothrombin (floats around the blood and is inactive) into thrombin
- prothrombin is a Vitamin K-dependent glycoprotein
- thrombin converts fibrinogen to fibrin (main protein in capuring platelets and making a blood clot)
describe the fourth stage of homeostasis
- clot dissolution (fibrinolysis)
- once tissue has repaired Factor XIIa (12) and/or tissue plasminogen activator (tPA) convert plasminogen to plasmin in the bloodstream
- plasmin breaks down (lyses) fibrin proteins (fibrin degradation products; FDPs)
- clot (thrombus) is dissolved and blood can flow normally within this repaired blood vessel
what are the 3 excessive bleeding disorders
- platelet deficiencies
acquired: thrombocytopenias (low platelet count; drug-induced, infection)
genetic: von willebrand’s disease (mutation in VWF gene) - coagulation deficiencies
acquired: vitamin K deficiency (multiple factors)
genetic: hemophilia A (factor VIII), hemophilia B (factor IX) - fibrinolytic hyperactivity
acquired: liver cirrhosis (↑ t-PA)
inherited: plasmin inhibitor deficiency
what are they 5 ways (drugs) to treat hemorrhagic disease?
- plasma fractions
- vitamin K
- desmopressin
- protamine sulfate
- aminocaproic acid (Amicar)
describe plasma fractions to treat hemorrhagic disease
fractionation of plasma (taken from the whole blood of healthy patients) to provide concentrated coagulation factors to patients who have:
- Hemophilia A (Factor VII deficiency: classic hemophilia)
- Hemophilia B (Factor IX deficiency; christmas disease)
- Von Willebrand’s disease (VWF deficiency)
- spontaneous deficiency of coagulation factors (5-10% of normal levels)
recombinant coagulation factors now available: eliminate need for plasma donation, reduce risk of infection
describe vitamin k to treat hemorrhagic disease
- vitamin k is essential for blood clotting; it’s required to produce prothrombin and is a cofactor for the biological activity of factors II, VII, IX and X
- low vitamin k levels are often found in:
- newborns: low levels at birth
- patients taking anticoagulants (warfarin - vitamin K antagonist)
- individuals with vitamin absorption disorders
- liver disease
- exist in two forms: vitamin K1 (phytonadione) found in food, vitamin K2 found in intestinal bacteria
- not used in the treatment of hemophilia
- treatment: IV or oral, depending on individual patient’s needs and health status
- IV route: give slowly (over 30 mins; risk of anaphylaxis); takes 2-4 hours to take effect (no known risk of anaphylaxis)
- considered very safe; no upper limit reported
- fat soluble vitamin: requires bile salts for absorption
describe desmopressin to treat hemorrhagic disease
- desmopression - anti-diuretic used to treat diabetes insipidus (replaces low ADH)
- desmopressin acetate (DDAVP) also used to treate mild hemophilia or von Willebrand’s disease by transiently increasing Factor VIII activity
- DDAVP activates signaling cascade in kidney cells that also induces exocytosis of VWF and Factor VIII from their storage sites
- available parenterally or a nasal spray if high doses are needed
describe protamine sulfate to treat hemorrhagic disease
- protamine sulfate (antagonist to heparin): used to treat heparin overdoses (heparin is a blood thinner)
- recombinant protein; binds to heparin, neutralizing its anti coagulant effects
- administered IV in situations of heparin overdose or to reverse heparin effects after coronary artery bypass surgery
- allergic reactions can be severe and include anaphylaxis
describe aminocaproic (amicar) to treat hemorrhagic disease
- aminocaproic (Amicar): fibrinolytic inhibitor
- during clot (thrombus) dissolution, plasmin binds to fibrin, resulting in lysis
- amicar is a synthetic drug that is similar to lysine → binds and blocks lysine binding site on plasmin → no lysis
- used in the treatment of fibrinolytic hyperactivity (such as after treatment with thrombi-busting drugs) or as adjunct therapy for hemophiliacs
what are most of the drugs in this class used to treat?
- most drugs in this class are used to treat patients with genetic deficiencies in coagulation OR to reverse anti-coagulant therapy or overdose
what is classic and aplastic anemia and their causes
classic anemia: characterized by a deficiency in red blood cells (RBCs) or hemoglobin leading to reduced oxygen transport to tissues
causes:
- iron deficiency
- vitamin deficiency
- RBC disorders
- chronic disease
aplastic anemia: bone marrow failure; deficiency of myeloid progenitors that give rise to RBCs and other immune cells
causes:
- cancer or cancer treatment
- sensitivity to chloramphenicol
growth factor Oprelvekin; IL-11 (Neumega) for anemia
Growth Factors
Oprelvekin; IL-11 (Neumega)
- Stimulates myeloid and lymphoid progenitor
cells and megakaryocytes to produce platelets
- Treatment for aplastic anemia as well as
severe thrombocytopenia (low platelet count) in patients treated with myelosuppressant chemotherapy drugs
