Hemostasis and Thrombosis

Question 1

hemostasis

Answer 1

ability to maintain blood in a FLUID state and prevent loss from sites of vascular damage

Question 2

what are the 3 major components of the hemostatic system

Answer 2

vascular wall, platelets and coag proteins

Question 3

pro-coag aspect in hemostasis (platelets) - primary hemostasis

Answer 3

vascular injry exposes subendothelial collagen –> ADHESION of platelets Gib protein receptor to vWF that connects to the collagen –> ACTIVATION recruits other platelets to the site, the platelets release messenger, alpha granules and dense bodies that change their shape from discs to flat plates and allow the contraction of the platelets –> AGGREGGATION where platelets begin binding through fibrinogen
** fibrinogen binding of platelets is not permanent

Question 4

pro-coag aspect hemostasis (coag cascade)- secondary

Answer 4

generation of thrombin that will convert fibrinogen to fibrin for stability
factor XIIIa will form the fibrin clot by crosslinking fibrin monomers

Question 5

whats one way to stop coagulation?

Answer 5

chelating Calcium, because it is in so many steps

Question 6

extrinsic pathway

Answer 6

clinically relevant

activation of factor VII by tissue factor

Question 7

what are the different pathways involved in fibrin clot formation

Answer 7

common (activates Xa to convert prothrombin to thrombin and fibrinogen to fibrin), intrinsic (leads to formation of factor IX) and extrinsic

Question 8

regulation of primary hemostasis

Answer 8

NO, prostacyclin and ADPase (regulate platelets)

Question 9

secondary hemostasis regulation

Answer 9

Antithrombins (and other serine protease inhibitors) –> form inactive complexes so fibrin is not formed
protein C pathway (controls V and VIII) –> APC + S cleaves factor V (disorders lead to hypercoag states)
fibrinolytic system (removes exess clot) –> endothelial cells release TPA that makes plasmin and degrades clots

Question 10

most important part of defining a cause for a bleeding disorder

Answer 10

clinical history

Question 11

prothrombin time (PT)

Answer 11

Time for plasma to form a clot
-Thromboplastin and Ca added
-EXTRINSIC cascade measured
Prolonged PT: issues w/ factors II/V/VII/X or fibrinogen (extrinsic pathway analysis in pts receiving coumadin/warfarin)

Question 12

INR

Answer 12

internal normalized ratio –> PT for comparison
Below 1: pt PT shorter than or equal to control (good) | Above 1: pt PT longer than control (bad)
**monitors anticoag pts.

Question 13

PTT (partial thromboplastin time)

Answer 13

INTRINSIC cascade
time for clot with added glass or kaolin, cephalin and ca
Prolonged: issues w/ factors VIII and others or fibrinogen (intrinsic pathway analysis in pts receiving heparin regimens - like prego women)

Question 14

platelet count

Answer 14

platlet number in anticoag blood
automated instrument used
Normal: 150,000 - 200,000 units/uL. Low = thrombocytopenia | High = thrombocytosis/thrombocythemia

Question 15

bleeding time

Answer 15

no longer used, replaced by PFA-100 (in vitro bleeding time so no more cuts)

Question 16

Mixing studies

Answer 16

If time corrects, deficiency. If time doesn’t correct, inhibitor present (ab that blocks normal factor or lupus)
if abnormal PT or PTT then add same amount of normal plasma…

Question 17

primary hemostasis disorders

Answer 17

Mucocutaneous bleeding/bleeding w/ trauma Prolonged bleed time and thrombocytopenia (low platelet count)

Question 18

secondary hemostasis disorders

Answer 18

Soft tissue bleeding or into joints /bleeding w/ trauma

Prolonged PT/PTT/thrombin times

Question 19

regulatory disorders with hemostasis

Answer 19

Soft tissue bleeding/bleeding w/ trauma
Normal in screening tests
ex. factor V leidin disorder

Question 20

Congenital bleeding disorders

Answer 20

• vWB, factor VIII defic (hemophilia A) and factor IX defic (hemophillia B)

Question 21

Factor VIII complex

Answer 21

vWF + favtor VIII + cofactor

-dissociates during clotting, factor VIII short half life without vWF (efficient complex)

Question 22

vWD

Answer 22

• autosomal dom
• quantitative (partial and total) or quality deficiency (3 types)
• most common inherited blood disorder (1% population)

Question 23

clinical presentation vWD

Answer 23

Mucocutaneous bleeding (nosebleeds, ecchymoses, excessive menstrual flow). 
Decreased VIII, prolonged bleed time, prolonged PTT

Question 24

Tx vWD

Answer 24

Mild: desmopressin (releases vWF in tissue) or antifibrinolytic agents
Severe: VIII concentrates and cryoprecipitates and recombination factor VIII (concentrates may include bld diseases)
symptoms may improve after puberty

Question 25

types of vWD

Answer 25

type 1- decreased about of vWF (most common)
tpe 2 - abnormal vWF
typ 3 - total absence vWF (aut recessive, most severe)

Question 26

Hemophilia A

Answer 26

x - linked recessive (males)

• deficiency of factor VIII
• recurrent soft tissue bleeding
• symtptoms start in early childhood

Question 27

Hemophilia A clinical

Answer 27

Recurrent soft tissue bleeding. Hemarthrosis, intramuscular hematomas, intracranial hemorrhage (30% due to spontaneous gene mutations), pseudotumors, intracranial bleeding and retroperitoneal bleeding
Normal bleed time, prolonged PTT, decreased VIII, normal vWF, normal IX.

Question 28

Hemophilia A classification

Answer 28

severe (less than 1% factor VII) –> recurrent spontaneous soft tissue and joint space bleeding (hemarthrosis)
moderate (1 to 5% factor VIII) –> bleeding with minor trauma
mild (more than 5% factor VIII) –> bleeding with major trauma

Question 29

therapy hemophilia A

Answer 29

Desmopressin and VIII concentrates, fibrinolytic inhibitors and recombinant factor VIII
-complications with therapy incude antibodies to factor VIII treatment, infectious diseases

Question 30

Hemophilia B

Answer 30

sex linked recessive

• deficiency of factor IX (similar presentation to hemophilia a)
• mild, mod or severe

Question 31

mechanims of thrombocytopenia

Answer 31

• decreased platelet produc
• increased destruciton, sequestered
• spontaneous bleeding when numbers below 20,000

Question 32

evaluation of thrombocytopenia

Answer 32

• clinical history and prolonged bleeding or hemorrhage (petechial)
• peripheral blood smear, bone marrow exam and platelet antibody determination

Question 33

Immune thrombocytopenia pupura (ITP) - child/acute form

Answer 33

• viral (cross reactivity from mimicry)
• sudden, severe onset
• spontaneous remission
• male and female equal

Question 34

ITP - chronic/adult

Answer 34

• no infection
• gradual, moderate onset
• infrequently remissed
• more common in females

Question 35

ITP pathopyhsio

Answer 35

autoantibodies against platelet membrane antigens, platelet protein receptor are common targets

• becasue antibody bound, sequesteration/destruction by the reticuloendothelial system increases
• a lot of megakaryotcytes in the bone marrow b/c trying to compensate for what is thinks are missing platelets

Question 36

ITP tx

Answer 36

Corticosteroids (to supress antibody formation), IV immunoglobin and splenectomy and immune suppression
** splenectomy sures ITP (can’t be sequestered)

Question 37

ITP clincal

Answer 37

petechial hemorrhages, ecchymoses and bleeding with trauma or surgery

Question 38

TTP (thrombotic thrombocytopenia purpura)

Answer 38

acute intravascular platelet activation with formation of platelet rich microthrombi in circulation due to eficiency in ADAMTS (metalloprotienase) that degrades large vWF

• inherited or aqcuired
• high mortality if untreated

Question 39

clinical TTP

Answer 39

Accumulation of large vWF. Fever, thrombocytopenia, microangiopathic hemoytic anemia (sheared RBC b/c of the increased amount of vWF making more platelets active and more microthrombi), renal failure, neurolgic changes.
Lab: thrombocytopenia, schistocytes in smear, anemia, reticulocytosis, normal coag parameters, increased bilirubin and LD. (intravasular hemolysis)

Question 40

DIC

Answer 40

acute unregulated widespread intavascular activation of hemostatic system. Systemic thrombin and plasmin formation. Coag factors are produced and consumed too fast = bleeding and microvascular thrombi = thrombocytopenia.
-Increased risk can be due to G- sepsis, snake bites, tissue injury (trauma/burn/surgery), malignancies, vascular lesions, hemolytic transfusion reactions, etc

Question 41

Tx DIC

Answer 41

remove stimulus and supportive care for patients coagulation reserve and transfusion therapy