Ch 4 Pathoma - Hemostasis and Related Disorders

Question 1

______ of the blood vessel is needed to carry blood to tissues. Damage to the wall is repaired by _____, which involves formation of a _____ at the site of vessel injury. It occurs in two stages (primary and secondary)

Answer 1

Integrity; hemostasis; thrombus (clot)

Question 2

Primary hemostasis forms a ____ ___-____ and is mediated by interaction between ___ and the _____.

Answer 2

weak platelet-plug; platelets; vessel wall

Question 3

Secondary hemostasis ____ the platelet plug and is mediated by the ____.

Answer 3

stabilizes; coagulation cascade

Question 4

Which stage of hemostasis forms a weak platelet plug?

Answer 4

primary hemostasis

Question 5

Which stage of hemostasis is mediated by the coagulation cascade?

Answer 5

secondary hemostasis

Question 6

Name the four steps of primary hemostasis.

Answer 6

1) Transient vasoconstriction of the damaged vessel; 2) Platelet adhesion to the surface of the disrupted vessel; 3) Platelet degranulation; 4) Platelet aggregation

Question 7

Step one of primary hemostasis, ______, is mediated by _____ and ____ release from endothelial cells.

Answer 7

transient vasoconstriction; reflex neural stimulation; endothelin

Question 8

In step 2 of primary hemostasis, _______, ____ binds exposed ____. Then platelets bind ____ using the ___ receptor.

Answer 8

platelet adhesion; Von Willebrand factor (vWF); subendothelial collagen; vWF; GPIb

Question 9

Von Willebrand factor is derived from _____ of endothelial cells and _____ of platelets.

Answer 9

Weibel-Palade bodies; alpha-granules

Question 10

Adhesion of platelets induces ____ and ____ with release of multiple mediators including ___ and ___.

Answer 10

shape change; degranulation; ADP; TXA2

step 3: platelet degranulation

Question 11

In step 3 of primary hemostasis, _____, ADP is released from platelet _____. It promotes the exposure of _____ receptor on platelets (needed for ____). Also, TXA2 is synthesized by platelet ____ and released. It also promotes ____.

Answer 11

platelet degranulation; dense granules; GPIIb/IIIa; platelet aggregation; COX; platelet aggregation

Question 12

Platelets aggregate at the site of injury via ____ using ___ (from plasma) as a linking molecule. This results in the formation of a ______. ____ helps stabilize it.

Answer 12

GPIIb/IIIa (ADP promotes exposure of the receptor); fibrinogen; weak platelet plug; coagulation cascade (secondary hemostasis)
(step 4: platelet aggregation)

Question 13

Disorders of primary hemostasis are usually due to abnormalities of _____. They can be divided into ____ or ____. Clinical features include ___ and ___ bleeding.

Answer 13

platelets; quantitative or qualitative; mucosal; skin

Question 14

Name the 6 symptoms of mucosal bleeding (and name the most common and most sever)

Answer 14

epistaxis (most common); hemoptysis; GI bleeding; hematuria; menorrhagia; intracranial bleeding (severe)

Question 15

Name the 4 symptoms of skin bleeding (and which one is a sign of thrombocytopenia and not usually qualitative disorders)

Answer 15

petechiae (1-2mm; quant, not qual); purpura (greater than 3mm); ecchymoses (greater than 1cm); easy bruising

Question 16

A normal platelet count is ____. Less than ___ leads to symptoms. A normal bleeding time is ____. Prolonged with qualitative or quantitative platelet disorders? Blood smear is used to assess ___ and ___ of platelets. BM bx used to assess ____.

Answer 16

150-400 K/microL; 50; 2-7 minutes; both!; number and size; megakaryocytes (produce platelets)

Question 17

_____ is an autoimmune production of ____ against platelet antigens (e.g. ____). It is the most common cause of thrombocytopenia in both ____ and ___.

Answer 17

Immune thrombocytopenic purpura (ITP); IgG; GPIIb/IIIa; children; adults

Question 18

In ITP (immune thrombocytopenic purpura), autoantibodies are produced by ____ in the ____. Antibody-bound platelets are consumed by ____ resulting in ____.

Answer 18

plasma cells; spleen; splenic macrophages; thrombocytopenia

Question 19

Acute ITP arises in ____ weeks after a ___ or ____. It is self-limited, usually resolving within days/weeks/months of presentation.

Answer 19

children; viral infxn; immunization; weeks

immune thrombocytopenic purpura

Question 20

Chronic ITP arises in ____, usually ____. May be ____ (unknown cause) or ____ (e.g. SLE). May cause short-lived thrombocytopenia in offspring because _____.

Answer 20

adults; WOCBP; primary; secondary; anti platelet IgG can cross the placenta

(immune thrombocytopenic purpura)

Question 21

Lab findings in ITP include high/normal/low platelet count (often ___); high/normal/low PT/PTT; high/low/normal megakaryocytic on bx.

Answer 21

low; less than 50; normal (coag factors not affected since this is a primary hemostasis disorder); high (bone marrow is trying to compensate for low platelets)

Question 22

Initial treatment for ITP is ____. ____ respond well; ____ may show early response but often relapse. ____ is used to raise the platelet count in symptomatic bleeding, but its effect is long/short. ____ eliminates the primary source of antibody and the site of platelet destruction (performed in ___ cases)

Answer 22

corticosteroids; children; adults; IVIg; short; splenectomy; refractory

Question 23

_____ is the pathologic formation of platelet microthrombi in small vessels. Platelets are ___ in the formation of microthrombi, and RBCs are ___ as they cross the microthrombi, resulting in ____ with ___.

Answer 23

Microangiopathic hemolytic anemia; consumed; sheared; hemolytic anemia; schisotcytes

Question 24

Microangiopathic hemolytic anemia is seen in these 2 disorders. Tx involves ___ and ____, particularly in ____.

Answer 24

Thrombotic thrombocytopenia purpura (TTP) and hemolytic uremic syndrome (HUS); plasmapheresis (remove autoantibody); corticosteroids (decrease production of autoantibody); TTP

Question 25

Thrombotic thrombocytopenic purpura (TTP) is due to decreased _____, an enzyme that normally cleaves ___ multimers into smaller monomers for degradation. The large uncleaved multimers lead to abnormal platelet ____ resulting in microthrombi

Answer 25

ADAMTS13; vWF; adhesion

Question 26

The decreased ADAMTS13 seen in TTP is usually due to an ______ most commonly see in female/male adults/children.

Answer 26

acquired autoantibody; female; adults

Question 27

Hemolytic uremic syndrome (HUS) is due to ____ damage by ___ or ____. It is classically seen in adults/children with _____, which results from exposure to ____.

Answer 27

endothelial; drugs; infxn; children; E coli O157:H7 dysentery; undercooked beef

Question 28

In HUS, E coli O157:H7 ____ damages ___ cells resulting in platelet microthrombi.

Answer 28

verotoxin; endothelial

Question 29

In which disorder resulting in microangiopathic hemolytic anemia is it more common to see renal insufficiency?

Answer 29

HUS (thrombi involve vessels of the kidney)

Question 30

In which disorder resulting in microangiopathic hemolytic anemia is it more common to see CNS abnormalities?

Answer 30

TTP (thrombi involve vessels of the CNS)

Question 31

Name the 5 clinical finding of HUS and TTP

Answer 31

1) skin/mucosal bleeding (plt micro thrombi use up plts); 2) microangiopathic hemolytic anemia (sheering of RBCs due to micro thrombi); 3) fever; 4) renal insufficiency (thrombi in kidney); 5) CNS abnormalities (thrombi in vessels of CNS)

Question 32

Lab findings in microangiopathic hemolytic anemia include high/normal/low platelet count; H/N/L bleeding time; H/N/L PT/PTT; H/N/L RBCs; H/N/L megakaryocytes

Answer 32

low; high (since low plts); normal (coagulation cascade not activated); low (anemia with schistocytes); high (compensating)

Question 33

Name four instances of qualitative platelet disorders

Answer 33

Bernard Soulier syndrome (GPIb defic); Glanzmann thrombasthenia (GPIIb/GPIIIa defic); aspirin (inactivates COX --> TXA2); uremia (plt funct)

Question 34

_____ is a qualitative platelet disorder due to a genetic deficiency in GPIb. ____ is impaired. Blood smear shows mild thrombocytopenia with ___ platelets

Answer 34

Bernard-Soulier syndrome; platelet adhesion; enlarged

Question 35

____ is due to a genetic GPIIb/IIIa deficiency. ____ is impaired.

Answer 35

Glanzmann thrombasthenia; platelet aggregation

Question 36

Aspirin reversibly/irreversibly inactivates ____, leading to lack of ___, which impairs ____.

Answer 36

irreversibly; COX; thromboxane A2; platelet aggregation

Question 37

____ disrupts platelet function and both ____ and ____ are impaired.

Answer 37

Uremia; adhesion; aggregation

Question 38

In secondary hemostasis, the coagulation cascade generates ____, which converts ___ in the weak platelet plug to ____, which is then cross-linked, yielding a stable ____. Factors of the coagulation cascade are produced by the ____ in an active/inactive state.

Answer 38

thrombin; fibrinogen; fibrin; platelet-fibrin thrmobus; liver; inactive

Question 39

Activation of coagulation cascade factors requires these three things.

Answer 39

exposure to an activating substance; phospholipid surface of platelets (since rxn occurs on platelet surface); calcium (derived from plt dense granules)

Question 40

____ activates factor VII (intrinsic/extrinsic pathway)

Answer 40

Tissue thromboplastin; extrinsic

Question 41

____ activates factor XII (intrinsic/extrinsic pathway)

Answer 41

sub endothelial collagen; intrinsic

Question 42

Disorders of secondary hemostasis are usually due to ___ abnormalities. Clinical features include ____ into muscles and joints and ____ after surgical procedures (circumcision and wisdom tooth extraction).

Answer 42

factor; deep tissue bleeding; rebleeding

Question 43

Prothrombin time (PT) measures intrinsic/extrinsic (factor(s) ___) and common (factors ____) pathways of the coagulation cascade

Answer 43

extrinsic; 7; 2, 5, 10 and fibrinogen

Question 44

Partial thromboplastin time (PTT) measures intrinsic/extrinsic (factor(s) ___) and common (factors ____) pathways of the coagulation cascade

Answer 44

intrinsic; 12, 11, 9, 8 2, 5, 10 and fibrinogen

Question 45

____ is a genetic factor VIII deficiency. It has ____ pattern of inheritance, though it can arise de novo.

Answer 45

Hemophilia A; x-linked recessive (so seen mostly in males)

Question 46

Hemophilia A presents with ___, ___, and ___ bleeding (classic of 2ndary hemostasis disorders). Lab findings include H/N/L PTT, H/N/L PT, H/N/L F8, H/N/L platelet count and H/N/L bleeding time. Tx involves ____.

Answer 46

deep tissue, joint, post surgical (severity depends on degree of deficiency); High PTT; normal PT; low F8; normal plt count (it has no effect on plts); normal bleeding time; recombinant F8

Question 47

Which disease has a genetic factor IX deficiency and what does it resemble?

Answer 47

Hemophilia B (aka Christmas disease); resembles hemophilia A except FIX levels are decreased instead of F8

Question 48

In coagulation factor inhibitor, there is a ___ against a coagulation factor resulting in impaired ____. Anti-factor ___ is most common.

Answer 48

acquired antibody; factor function; 8 | clinically similar to hemophilia A

Question 49

How do you tell the difference between coagulation factor inhibitor and hemophilia A?

Answer 49

Mixing study: PTT does not correct upon mixing normal plasma w/pt's plasma due to inhibitor (in hemophilia A, PTT does correct)

Question 50

What is the most common inherited coagulation disorder, and what is the most common type of inheritance?

Answer 50

Von Willebrand Disease; autosomal dominant (decreased vWF) | there are multiple subtypes, causing both quantitative and qualitative defects - most common is above

Question 51

Von willebrand disease presents with mild __ and __ bleeding, since low vWF impairs platelet ___. Tx is ___, which increases vWF release from ___ of ___ cells

Answer 51

mucosal; skin; adhesion; desmopressin (ADH analog); Weibel Palade bodies; endothelial

Question 52

Lab findings for Von Willebrand disease include H/N/L bleeding time, H/N/L PTT, H/N/L PT. And what is seen on the ristocetin test?

Answer 52

high bt; high PTT (since vWF normally stabilized F8); normal PT; abnormal ristocetin test

Question 53

In the ristocetin test, ristocetin induces platelet agglutination by causing __ to bind platelet ___. With a lack of the former --> impaired agglutination --> abnormal test.

Answer 53

vWF; GPIb

Question 54

vWF can stabilize coagulation cascade factor ____. Without it, you see a decreased half life of the factor

Answer 54

8

Question 55

Vitamin K is activated by ___ in the ___. Activated vitamin K ____ factors ___ and proteins ___ (this is needed for factor function).

Answer 55

``` epoxide reductase (coumadin blocks this enzyme); liver; gamma carboxylates; 2, 7, 9, and 10; C and S (defic disrupts funct of multiple coag factors) ```

Question 56

Vitamin K deficiency occurs in these three cases.

Answer 56

Newborns (lack of GI colonization by vit K producing bacteria --> give injection to prevent hemorrhage); long term antibiotic therapy (can kill GI bacteria); malabsorption (leads to deficiency of fat soluble vit = DEAK)

Question 57

Liver failure can cause abnormal secondary hemostasis because of decreased __ and __ of coagulation factors. The effect of liver failure on coagulation is followed using __

Answer 57

production; activation (decreased activation of vitamin K by epoxide reductase); PT (makes sense since vit K is involved more in activating PT factors - coumadin effect is seen on PT factors)

Question 58

The heparin effect is measured using ___.

Answer 58

PTT (HEP effect --> 3 letters like PTT)

Question 59

The coumadin effect is measured using ___.

Answer 59

PT (coumadin blocks epoxide reductase, involved in activating 2, 7, and 10 (also 9))

Question 60

___ can cause abnormal secondary hemostasis by diluting coagulation factors resulting in a relative deficiency

Answer 60

large volume transfusion

Question 61

___ is platelet destruction that arises secondary to heparin therapy. Caused when the pt develops ___ against Heparin - ___ complex. This may lead to activation of remaining platelets leading to ___.

Answer 61

Heparin-Induced Thrombocytopenia (HIT); IgG autoantibodies; platelet factor 4; thrombosis

Question 62

___ is pathologic activation of the coagulation cascade. The widespread micro thrombi results in __ and __. Consumption of platelets and factors results in ___, especially from ___ sites and ___ surfaces.

Answer 62

Disseminated Intravascular Coagulation (DIC); ischemia; infarction; bleeding; IV; mucosal (bleeding from body orifices)

Question 63

Name the 5 disease processes that classically cause DIC and what about it activates coagulation.

Answer 63

Obstetric complications (tissue thromboplastin in the amniotic fluid activates it); Sepsis (endotoxins from bacterial wall and cytokines induce endothelial cells to make tissue factor); Adenocarcinoma (mucin activates coag); APL (primary granules (form Auer rods) activate coag); Rattlesnake bite (venom)

Question 64

DIC caused by sepsis is seen especially with these two bacterial infections and these two cytokines.

Answer 64

E coli or N meningitidis; TNF and IL-1

Question 65

Lab findings for DIC include H/N/L platelet count, H/N/L PT, H/N/L PTT, H/N/L fibrinogen. Name two other common lab findings

Answer 65

low platelet count (plts are consumed); high PT and PTT (factors are consumed); low fibrinogen (consumed since lots of clots); microangiopathic hemolytic anemia (shearing of RBCs passing thrombi); elevated fibrin split products (esp D-dimer)

Question 66

What is the best screening test for DIC?

Answer 66

elevated D-dimer (caused by lysing of clots - derived from splitting of cross-linked fibrin, not fibrinogen!)

Question 67

Tx for DIC involves these three things

Answer 67

treating the underlying cause; transfusion of blood product; cryoprecipitate (contains coag factors)

Question 68

Normal ___ removes thrombus after damaged vessel heals. ___ converts plasminogen to plasmin, which then cleaves ___ and ___, destroys ___, and blocks ____. ___ inactivates plasmin.

Answer 68

fibrinolysis; tissue plasminogen activator (tPA); fibrin; serum fibrinogen; coagulation factors; platelet aggregation (plasmin shuts down ability to form a clot AND lyses the already existing clots); alpha2-antiplasmin

Question 69

Disorders of fibrinolysis are due to ____ resulting in excessive cleavage of ___. Name two examples and how they cause it.

Answer 69

plasmin overactivity; serum fibrinogen; Radical prostatectomy (release of urokinase activates plasmin); cirrhosis of liver (reduced production of alpha2-antiplasmin)

Question 70

How do you tell apart disorders of fibrinolysis and DIC when both present with bleeding?

Answer 70

disorders of fibrinolysis have a normal platelet count and D-dimers are not formed since fibrin thrombi are absent (DIC has decreased plts and elevated D-dimer_

Question 71

Lab findings of disorders of fibrinolysis include H/N/L PT, H/N/L PTT, H/N/L bleeding time, H/N/L plt count. You also see increased ____ with/without D-dimers.

Answer 71

high PT and PTT (plasmin destroys coag factors); high bleeding time (plasmin block plt aggregation); normal plt count; fibrinogen split products; without

Question 72

In disorders of fibrinolysis, serum fibrinogen is lysed, but D-dimers are not formed since ___ are absent. Tx is ___, which blocks activation of ____.

Answer 72

fibrin thrombi; aminocaproic acid; plasminogen