Unit 05 Blood disorders: Hemorrhagic disease

Question 1

what is hemostasis

Answer 1

• proces that keeps blood fluid and clot free in normal vessels and forms localized plug in injudred vessels
• blood clot in injured vessels are essential to prevent blow flow and allow healing, must be localized to prevent widepsread clotting within intact vessels

*goal of hemostasis = preventing prolonged hemorrhage and spontaneous thrombosis

Question 2

what are prothrombogenic factors

Answer 2

platelet activators, procoagulants, vasocontriction and fibrinolytic inhibitors

Question 3

what are anti-thrombogenic factors

Answer 3

platelet inhibitors, anticoagulants, vasodilators, fibrinolytic activators

Question 4

describe the first stage of hemostasis

Answer 4

• vascular spasm or localized vasocontriction is the response to injury
• damaged vessel immediately constricts in order to restrict or reduce blood flow to reduce blood loss
• occurs due to secretion of endothelium derives vasoconstrictors like endothelin
• sympathetic and local factors (thromboxane) are also released which initiates the myogenic properties in the vessel wall and induces smooth muscle contraction

Question 5

what is the second step of hemostasis

Answer 5

primary hemostasis

• after vasoconstriction, platelets activate forming initial plug
• platelets adhere to exposed collagen of damaged endothelium and to each other
• platelet plug releases chemical mediators (TXA2, 5-HT, and ADP) - recruite more paltelets, promoting vasoconstriction and initiating coagulatino cascade

*goal of other two stages is to form a stable permanent plug

Question 6

describe step 3 of hemostasis

Answer 6

secondary hemostasis (aka coagulation cascade)

• sequential conversion of inactive proteins into catalytically active proteases
• activated endothelium and other nearby cells express tissue facor (membrane bound coagulant factor) - complexed w/ coagulation factor VII to initiate the coagulation cascade
• result = activation of thrombin (critical enzyme)
• thrombin converts soluble fibrinogen to an insoluble fibrin polyer that forms the matrix of the clot

Question 7

describe stage 4 of hemostasis

Answer 7

• final stage = fibrinolysis
• involves clot dissolution
• needed for wound healing and resoration of vessel flow
• process of fibrinolysis involves proteolytic actions of plasmin bound to the clot

Question 8

what are the 4 stages of hemostasis?

Answer 8

1. Vasoconstriction
2. primary hemostasis (forms temporary paltelet plug)
3. secondary emostasis (better clot)
4. fibrinolysis and clot dilution

Question 9

describe the coagulation cascade

Answer 9

• divided into intrinsic, extrinsic pathway adn common pathway
• intrinsic and extrinsic pathways converge at the level of factor X activation
• intrinsic pathway largely in vitro and extrinsic majorly in vivo coagulation.
• extrinsic is initiated at sites of vascular injury by expression of tissue actor on several diff cell types - inc endothelial cells, activated leukocytes (and leukocyte microparticles), subendothelial vascular smooth muscle cells, and subendothelial fibroblasts.

Question 10

what are hemorrhagic diseases characterized by?

Answer 10

bleeding

may be caused by several factors that regulate hemostasis

Question 11

what is thrombocytopenia

Answer 11

platelet deficiency

• decrease in paltelet production

Question 12

what is von Willebrand disease?

Answer 12

qualitative genetic defect of the platelets

Question 13

what can cause excessive bleeding

Answer 13

clotting factor deficiencies involving a single factor (such as VIII or IX and resulting in hemophilia) or multiple factors (vitamin K deficiency)

Question 14

what is fibrinolytic hyperactivity

Answer 14

another disease that can disregulate hemostasis

Question 15

What are treatments for hemorrhagic diseases

Answer 15

• vitamin K, antifibrinolytic agents, blood products (replacement factors) and many others

Question 16

what are the two forms of vitamin K

Answer 16

• exists in 2 natural forms
• Vit K1 aka phytonadinone sounf in leafy greens and vegetables
• Menaquinone found in intestinal bacteria

Question 17

describe the role of vitamin K in clotting

Answer 17

• serves as a cofactor for biological activivty of factors II, VII, IX, and X throughout post translational modifcation

Question 18

Vitamin K as a drug

Answer 18

• prescribed to treat anticoagulant toxicity, vitamin K deficiency, and prevent hemorragic disease in newborns
• available for oral and parenteral use but must be given slowly via intraentous route to avoid anaphylaxis
• requires approx 6 hours to exhibit effects and is considered very safe
• fat soluble, so requires bile salts for intestinal absorption

Question 20

What are antifibrinolytics

Answer 20

aka fibrinolytic inhibitors

• common pharmacological agents used to treat hemorrhagic disease
• since fibrinolysis occurs when plasmin lyses fibrin and fibrinogen, antifibrinolytics work as agonists on lysine binding site on plasmin, locking ability to bind to fibrin

Question 21

aminocaproic acid

Answer 21

aka amicar

• synthetic agent simialr to lysine and binds to lysine bidning site
• competitively inhibits the action of plasmin on fibrin

*incomplete lysis of drug can cause thrombi formation which can be dangerous

• fibrinolyic inhibtors are effective in treatment of bleeding disorders such as bleeding from fibrinolytic therapy ro as adjunct therapy for hemophiliacs

Question 22

plasma fractions

Answer 22

• form of blood products (treatment)
• used to treat deficiencies in plasma coagulation factors that can cause bleeding and will spontaneously occur when fractions are 5-10% less than normal levels
• plasma coagulation dificiencies include: factor VIII deficiency resulting in hemophilia A (classic hemophilia) and factor IX deficiency resulting in hemophilia B (Christmas disease).
• to treat those plasma factors can be isolated from blood (fractionation) and concentrated so they can be administered

Question 23

Desmopressin acetate (DDAVP®)

Answer 23

antidiuretic

transiently increases factor VIII activity in mild hemophilia or von Willebrand’s disease.

available in injectable form or a nasal spray if high doses are needed.

Question 24

protamine sulfate

Answer 24

• generic drug from salmon sperm
• used to treat heparin overdoses bc it binds to heparin, neutralizing the anticoagulant effects
• agent is given slowly through intravenous route to avoid collapse of vessels
• high doses can produce anticoagulant effects so the patient needs to be monitored