Coagulative Disorders

Question 1

Platelets

Answer 1

Adhesion -> Activation -> Aggregation

Question 2

Coagulation

Answer 2

Activation -> Thrombin formation -> Fibrin formation, polymerization and stabilization

Question 3

Primary Hemostasis:

Secondary Hemostasis:

Answer 3

Platelet plug formation.

Fibrin Clot Formation

Question 4

Primary Hemo = Platelet response to vascular injury.

Membrane Receptor:

Adhesive Protein:

Appropriate Surface:

Answer 4

Glycoprotein 1b

von Willebrand Factor (vWF)

Subendothelial matrix (collagen)

Question 5

Platelet activation:

Secretion = _____ and ____

Activation of ______ receptor

_______ reorganization

Shape Change - ____ to ____ (_____)

Answer 5

alpha-granules and dense bodies.

GP 2b/3b receptor

Phospholipid

Rounded discs to flat plates = Increased surface area

Question 6

Platelet Aggregation

Answer 6

GP 2b/3a bind to fibrinogen with ADP = Fibrin

Question 7

Fibrin Clot formation (2ndary Hemostasis):

Formation of _____

Formation of ____ _____ (with crosslinking of ____ by ______)

Answer 7

Thrombin

Fibrin clot

fibrin, factor 13a

Question 8

Intrinsic Pathway:

Activation of Factor ____ by _____, followed by activation of Factor ____ by factor _____. Factor ____ activates Factor _____

Answer 8

12 by kallikrein.

11 by Factor 12a

Factor 11a activates Factor 9

Question 9

Extrinsic Pathway:

Sequence of activation of Factor _____ by ______

Answer 9

Activation of Factor 7

By Tissue Factor

Question 10

Common Pathway:

Activation of Factor ____ by ____ followed by conversion of ______ to ______, followed by conversion of ______ to ______

Answer 10

10 by 10a.

Prothrombin (II) to thrombin.

Fibrinogen (I) to Fibrin monomors

Question 11

Fibrin Clot:

Formed when fibrin monomers generated by _____ polymerize. Made more stable by covalent crosslinking by factor _____

Answer 11

Thrombin.

Factor 13

Question 12

Primary HemoStasis Regulation

Answer 12

NO, Prostacyclin PGI2, ADPase

Question 13

Secondary Hemostasis Regulation

Answer 13

Antithrombin.
Protein C pathway (controls 5a and 8a).
Fibrinolytic system (excess clot)

Question 14

Anti-Thrombins = _____ + ______

Answer 14

Serine Protease plus SERPIN

Question 15

Antithrombin III:

In presence of ______ becomes activated so that it can _____

Answer 15

Heparin, complexes with thrombin = stops fibrin monomer production

Question 16

Protein C System:

Activated Protein C plus ______ serve to inactivated ____ and _____

Answer 16

Protein S.

5a, 8a

Question 17

Protein C or S deficiencies = ______.

Factor 5 leiden mutation promotes ______ due to _____

Answer 17

Hypercoaguable states.

Coagulation. Resistance to enzymatic inactivation by Protein C/S complex.

Question 18

Plasmin = _______

Answer 18

Removes excess fibrin clot by chopping it into FDPs

Question 19

Prothrombin Time (PT)

Screens or activity of ______.

_____ and ____ are added to patient’s plasma with ____

Answer 19

Extrinsic Pathway (Factors 2, 5, 7, 10, fibrinogen)

Phospholipid, tissue factor, Calcium

Question 20

Prothrombin Time (PT):

Forms basis of ______ (______)

11-13 seconds

Answer 20

International Normalized Ratio (INR)

Patient/control ratio = 0.8-1.2

Used to monitor patients on warfarin

Question 21

Partial Thromboplastin Time (PTT)
Screens for activity within _______

___ - ___ seconds

Answer 21

Intrinsic pathway (factors 12 activated, 11, 9, 7, 10, 5, 2 and fibrinogen)

28-35

Question 22

Disorders of Primary Hemostasis:

Clin Manifestations

Lab Findings

Answer 22

Mucocutaneous bleeding, petechial.
Excessive bleeding w/ trauma.

Prolonged BT/PFA-100, thrombocytopenia

Question 23

Secondary hemostasis disorders
Clin mani
Lab findings

Answer 23

Soft tissue bleeding and excessive bleeding with trauma.

Prolong PT and PTT and TT

Question 24

Regulatory Disorders of Hemostasis

Clinical Manif

Lab Manifes

Answer 24

Soft tissue bleeding, excessive bleeding with trauma.

Normal PT and PTT, normal bleeding time, normal platelet count

Question 25

Congenital Bleeding Disorders

Answer 25

Von willebrand dz, factor 8 deficiency, factor 9 deficiency

Question 26

Von Willebrand Dz _______ disorder Due to _______ ________ is the dominant clinical manisfestation

Answer 26

Autosomal dominant. abnormalities in vW factor Mucocutaneous bleeding

Question 27

Classification of vWD Type 1 = Type 2 = Type 3 =

Answer 27

Quantitative deficiency (partial) Qualitative deficiency Quantitative deficiency (total)

Question 28

vWD Clinical Manifestations

Answer 28

Epistaxis, ecchymoses, mucosal bleeding

Question 29

vWD Lab Features ``` BT/PFA-100: PTT: VIII: vWF:ag: vWF:Rcof: ```

Answer 29

``` Prolong Usually prolonged decreased to normal decreased to normal decreased to normal ```

Question 30

Hemophilia A: ______ disorder Deficiency in ______ Recurrent ______ Usually start in ____ Therapy =

Answer 30

X-linked recessive Factor 8 Soft tissue bleeding Early childhood Factor 8 concentrates

Question 31

Hemophilia A Clinical Manifestations ____, _____ bleeding, _______ w/ trauma, _______ hematomas, ______ ______

Answer 31

``` Hemarthrosis Soft tissue Excessive bleeding Intramuscular Intracerebral hemorrhage ```

Question 32

Lab Features of Hemophilia A ``` BT/PFA-100 PTT Factor VIII vWF:ag: vWF:Rcof: Factor 9: ```

Answer 32

``` normal prolonged decreased normal normal normal ```

Question 33

Hemophilia classification ``` Severe = ____% factor 8 Moderate = ___ % factor 8 Mild = ____% ```

Answer 33

Less than 1%. 1-5% More than 5%

Question 34

Hemophilia B: _____, ____ disorder Defiency in _____ Similar presentation as factor 8 Treatment =

Answer 34

Sex-linked, recessive Factor 9 Factor 9 Concentrates

Question 35

Mechanisms of Thrombocytopenia

Answer 35

Decreased platelet production Increased destruction Sequestration Congenital vs acquired

Question 36

Immune Thrombocytopenic Purpura (ITP) Acute = _____ ______ common ____ Thrombocytopenia Frequent ______ M:F ratio ____

Answer 36

Childhood. Viral prodrome. Severe spontaneous remission 1:1

Question 37

Chronic ITP Seen in ______ No ______ ____ onset _____ thrombocytopenia ______ spontaneous remission M:F ratio _____

Answer 37

Adults No antecedent infection Gradual Moderate Infrequent More common in females

Question 38

ITP Pathophysiology Autoantibodies targeted at ______ ____ and ____ common targets ______ bound to surface = ______/______ by _____

Answer 38

Platelet membrane antigens GP Ib and 2b/3a IgG, sequestration/destruction by reticuloendothelial system

Question 39

ITP clinical features

Answer 39

Petechial hemorrhages, gingival bleeding, ecchymoses, bleeding with trauma/surgery

Question 40

ITP Bone Marrow and blood findings: _______ normal to increased ________ changes on blood smear review Treatment

Answer 40

Megakaryocytes No microangiopathic Corticosteroids, IV ig, immunosuppresion, splenectomy

Question 41

Thrombotic Thrombocytopenic Purpura (TTP) ____ disorder characterized by _______ with formation of ______ throughout circulation Due to defiency of _____, a MMP that degrades _____ Can be ____ or ______ Untreated = ____

Answer 41

Acute disorder intravascular platelet activation platelet-rich microthrombi ADAMTS 13, vWF Inherited or acquired High mortality

Question 42

DIC: Systemic formation of ____ and ____ with simultaneous _____ formation and consumption of ____ that promotes _____

Answer 42

Thrombin, plasmin Microthrombi Clotting factors Bleeding

Question 43

DIC Clinical settings

Answer 43

Infections by gram negative sepsis Tissue injury Obstetrical complication Malignancies

Question 44

DIC Clinical manifestations

Answer 44

Bleeding from multiple sites Thromboembolic problems Hypotension and shock

Question 45

DIC therapy FFP = Cryoprecipitates = ______

Answer 45

Coagulation and regulatory proteins Fibrinogen, Factor 8, vWF Platelets