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STEP 6: HemeOnc PATHOMA > Hemostasis and Related Disorders > Flashcards

Hemostasis and Related Disorders Flashcards

1
Q

What are the two important molecules inside WEIBEL-PALADE bodies responsible for endothelial function?

A

W: vWF (role in hemostasis)
P: P-selectin (role in inflammation)

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2
Q

What are the two sources of vWF?

A
  1. WEIBEL-PALADE bodies of ENDOTHELIAL cells

2. alpha granules of PLATELETS

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3
Q

Do quantitative platelet disorders (thrombocytopenia) or qualitative platelet disorders show PETECHIAE?

A

QUANTITATIVE PLATELET - i.e. THROMBOCYTOPENIA

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4
Q

What is the most common cause of THROMBOCYTOPENIA in children and adults? What is the pathophysiology?

A

IMMUNE THROMBOCYTOPENIC PURPURA (ITP) -
Spleen plasma B cells produce IgG AutoAbs -> IgG Ab bind GPIIb/IIIa receptors on PLT -> Ab-bound PLTS are then CONSUMED by splenic macrophages
**Spleen = makes + consumes plasma cell IgG

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5
Q

Which age population is CHRONIC IMMUNE THROMBOCYTOPENIC PURPURA most prevalent in? Which disease state is a SECONDARY cause of chronic ITP?

A

Women of child-bearing age

SLE (Lupus) is an important secondary cause of ITP

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6
Q

What are the three treatment plans in order of severity for IMMUNE THROMBOCYTOPENIC PURPURA?

A
  1. Corticosteroids - Effective moreso in the acute form classically seen in children
  2. IVIG - To overrun the splenic macrophages system to consume the IVIGs rather than IgG-bound to platelets (EFFECT IS SHORT-LIVED: Mainly to fend off a fatal complication of intracranial hemorrhage)
  3. SPLENECTOMY - Remove primary source of IgG + site of destruction (ONLY in refractory cases)
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7
Q

Helmet, sheared RBC on blood smear

A

SCHISTOCYTE

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8
Q

What are the two etiologies of microangiopathic hemolytic uremia?

A

TTP: Thrombotic thrombocytopenic purpura
HUS: hemolytic uremic syndrome

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9
Q

What enzyme is deficient in TTP? What does it do?

A

ADAMTS13 - Enzyme that breaks down vWF multimers into smaller monomers for eventual degradation

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10
Q

Who is the most common population affected by thrombotic thrombocytopenic purpura? What is the most common means of acquiring TTP?

A

ADULT FEMALES with an autoimmune disease who acquired autoAb against ADAMTS13

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11
Q

Who is the most common population affected by hemolytic uremic syndrome? What is the most common means of acquiring HUS?

A

CHILDREN

After exposure to uncooked meat -> Acquiring E.coli O157:H7 infection and e.coli VEROTOXIN -> Damages endothelial cells -> PLT microthrombi -> RBC get sheared while passing through -> SCHISTOCYTES

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12
Q

Which infection causes hemolytic uremic syndrome? What is the toxin?

A

E.Coli O157:H7

E.Coli VEROTOXIN

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13
Q

Which system is predominantly affected by HEMOLYTIC UREMIC SYNDROME?

A

Renal insufficiency

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14
Q

Which system is predominantly affected by THROMBOTIC THROMBOCYTOPENIC PURPURA?

A

CNS Abnormalities

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15
Q

How do IMMUNE THROMBOCYTOPENIC PURPURA and MICROANGIOPATHIC HEMOLYTIC ANEMIA differ in terms of lab findings?

A

SAME except for the presence of schistocytes and anemia in MICROANGIOPATHIC HEMOLYTIC ANEMIA

SAME FINDINGS: Thrombocytopenia, Increased bleeding time, Normal PT/PTT, Megakaryocyte hyperplasia on bone marrow

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16
Q

What is the treatment plan for MICROANGIOPATHIC HEMOLYTIC ANEMIA, particularly due to THROMBOTIC THROMBOCYTOPENIA PURPURA?

A
  1. PLASMAPHERESIS: Removes proteins from blood and thus removes autoAb against ADAMTS13
  2. CORTICOSTEROIDS - Decrease overall Ab protein prdn
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17
Q

Which qualitative platelet disorder impairs PLATELET ADHESION ONLY (specifically GP1b deficiency)?

A

BERNARD SOULIER SYNDROME

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18
Q

Which qualitative platelet disorder impairs PLATELET AGGREGATION by affecting degranulation process (specifically lowers TXA2 levels)?

A

ASPIRIN TOXICITY

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19
Q

Which qualitative platelet disorder impairs PLATELET AGGREGATION ONLY (specifically GPIIb/IIIa deficiency)?

A

GLANZMANN THROMBASTHENIA

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20
Q

Which qualitative platelet disorder impairs BOTH PLATELET AGGREGATION and ADHESION?

A

UREMIA -Poor kidney function -> Buildup of nitrogenous waste

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21
Q

What is the major difference in sites of bleeding between disorders of primary hemostasis versus those of secondary hemostasis?

A

PRIMARY HEMOSTASIS DISORDERS - Mucosal (particularly epistaxis) + Skin bleeding

SECONDARY HEMOSTASIS DISORDERS - Deep tissue and joint bleeding, re-bleeding after surgical procedures

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22
Q

INTRINSIC PATHWAY

A

PTT (More letters than PT, More coagulation factors involved), SEC (subendothelial collagen), HEP (3 letter pattern, more accurate measurement of effect of heparin than coumadin)

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23
Q

EXTRINSIC PATHWAY

A

PT, TT (Tissue thromboplastin factor), Coumadin

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24
Q

What is the inheritance pattern of HEMOPHILIA A? What factor is deficient in this d/o?

A

X-linked recessive
Generally mother is asymptomatic with the grandfather having a tendency to bleed (hemophilia)
HEMOPHILIA AAAEIGHT = DEFICIENCY OF factor EIGHT

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25
Q

What are the lab findings of HEMOPHILIA A?

A

INCREASED PTT, Normal PT
DECREASED Factor VIII
Normal platelet count (150-400K), Normal bleeding time (5-7min)

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26
Q

What is the Tx of HEMOPHILIA A

A

Recombinant FVIII

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27
Q

Is family history a requirement for HEMOPHILIA A?

A

No, it can also arise from a de novo mutation

28
Q

What is the difference between HEMOPHILIA A and HEMOPHILIA B

A

SAME LAB and CP except for DECREASED FACTOR IX - Hemophilia B

29
Q

What is the most common coagulation factor inhibitor disorder?

A

FACTOR VIII COAGULATION FACTOR INHIBITOR

30
Q

What is the pathological difference between FACTOR VIII INHIBITOR DISORDER and HEMOPHILIA A?

A

HEMOPHILIA A - Genetic deficiency of Factor VIII

FACTOR VIII INHIBITOR DISORDER - Autoimmunization (AutoAb formation) against FVIII

31
Q

How do you clinically differentiate between FACTOR VIII INHIBITOR DISORDER and HEMOPHILIA A?

A

MIXING STUDIES - Mixing pt’s plasma with normal plasma
HEMOPHILIA A - PTT DOES CORRECT bec replenishment via normal plasma is sufficient enough to reduce PTT back to normal

FACTOR VIII INHIBITOR DISORDER - PTT DOES NOT CORRECT bec autoAbs will immediately neutralize the normal plasma FVIII

32
Q

What is the most common INHERITED Genetic coagulation disorder?

A

VON WILLEBRAND DISEASE

33
Q

What is the most common type of VON WILLEBRAND DISEASE?

A

AUTOSOMAL DOMINANT VON WILLEBRAND DISEASE

34
Q

Do pts with von willebrand disease present with mucosal/skin bleeding or deep tissue/joint bleeding? Why?

A

MUCOSAL + SKIN BLEEDING - vWF necesssary for PLATELET ADHESION via GPIb-binding to exposed sub-endothelial collagen. Deficiency of this will result in impaired primary hemostasis

Although vWF is involved in secondary hemostasis via Factor VIII, the deficiency is not enough to manifest clinically. Enough to manifest in labs (ELEVATED PTT)

35
Q

What is the lab data of VON WILLEBRAND DISEASE? Include bleeding time, PTT and PT

A

INCREASED bleeding time - due to impaired primary hemostasis (specifically platelet adhesion)
INCREASED PTT - due to impaired Factor VIII stability with loss of vWF
NORMAL PT - Not involved in extrinsic pathway

36
Q

What specific test further strengthens VON WILLEBRAND DISEASE?

A

ABNORMAL RISTOCETIN TEST (No platelet aggregation because vWF is lacking)

37
Q

**What is the treatment plan of VON WILLEBRAND DISEASE?

A

**DESMOPRESSIN - Induces vWF release from Weibel palade bodies of endothelial cells

38
Q

Which coagulation factors/anti-coagulant factors need VitaminK?

A

FACTORS 2, 7, 9, 10

PROTEINS C, S

39
Q

How is Vitamin K activated? What is its action on Factors 2,7,9,10,C,S?

A

VitK comes in through the gut -> Goes into the liver -> Gets activated by hepatic EPOXIDE REDUCTASE -> Activated VitK gamma carboxylates factors 2,7,9,10,c,s

40
Q

What drug inhibits EPOXIDE REDUCTASE and thus inhibits VitK activation?

A

COUMADIN

41
Q

What are 3 situations in which someone can become VitK deficient?

A
  1. NEWBORNS - Not fully developed gut with bacteria colonized. No bacteria = No VitK generation
  2. LONG TERM ANTIBIOTIC THERAPY - Kill off gut flora
  3. MALABSORPTION - Unable to absorb fat-soluble vitamins (A,D,E,K)
42
Q

Which lab data value is used to measure the effect of liver failure on coagulation? Why does it manifest this way?

A

PT**

Technically, PT and PTT will both be elevated in liver failure BUT PT is more sensitive and will be elevated first because Factor VII (representative of PT extrinsic pathway) has the shortest half-life and thus will be the first test to become abnormal

LIVER major site of coagulation factor production + epoxide reductase production (which activates VitK - co-factor needed for 2,7,9,10,C,S)

43
Q

DDx of seeing SCHISTOCYTES in blood smear

A

PRESENCE OF MICROTHROMBI WITHIN VASCULATURE:

  1. DIC - DISSMEINATED INTRAVASCULAR COAGULOPATHY
  2. TTP - THROMBOTIC THROMBOCYTOPENIC PURPURA
  3. HUS - HEMOLYTIC UREMIC SYNDROME
  4. HELLP- HEMOLYSIS ELEVATED LIVER ENZYME LOW PLATELET
44
Q

Describe the pathogenesis of HEPARIN-INDUCED THROMBOCYTOPENIA.

A

HEPARIN develops a complex with PLATELET FACTOR 4 = HEP-PF4

Pt develops IgG autoAbs against HEP-PF4 complex -> Splenic macrophages consume these platelets -> THROMBOCYTOPENIA

45
Q

What is the major complication of worry in HIT?

A

THROMBOSIS (Formation of blood clot within a BV - in this case, fragment of destroyed PLT activating remaining PLTs)

Result = Subsequent ischemia/infarction of tissues

46
Q

What is the treatment for cases in which thrombosis results from HIT? What medication is CONTRAINDICATED?

A

Stop heparin + administer another anti-coagulant

Can NOT be COUMADIN (i.e. WARFARIN) - Due to high risk of coumadin-induced skin necrosis

47
Q

What are the two pathologic consequences of DIC?

A

1) Massive thrombi (blood clot within BV) in small blood vessels -> ISCHEMIA + INFARCTION of tissues
2) Massive thrombi formation - Consumes a lot of coagulation factors and platelets -> BLEEDING from IV sites/mucosal areas (lungs, mouth, GI tract)

48
Q

Is DIC a primary condition or secondary condition?

A

ALWAYS SECONDARY

49
Q

How can DIC result from an obstetric complication?

A

Amniotic fluid contains TISSUE THROMBOPLASTIN (TISSUE FACTOR) -> Leaks into mother’s circulation -> Coagulation cascade activation

50
Q

How can DIC result from sepsis?

A

MECH 1) Bacterial ENDOTOXIN from cell wall activates coagulation cascade
MECH 2) Reactive inflammatory response to infection -> Macrophages produce IL-1 + TNF-alpha -> activates coagulations cascade (particularly HAGEMAN FACTOR [Factor XII])

51
Q

How can DIC result from adenocarcinoma?

A

Adenocarcinoma -> MUCIN release -> activates coagulation cascade

52
Q

How can DIC result from APL?

A

Release of PRIMARY GRANULES from acute promyelocytes into circulation -> activates coagulation cascade

53
Q

How can DIC result from rattlesnake bite?

A

Venom from the rattle snack bite enters circulation -> Activates coagulation cascade

54
Q

What are the lab findings of DIC? (Include platelet ct, PT/PTT, fibrinogen)

A
  1. DECREASED PLATELET CT (thrombocytopenia) - Platelets being used up for thrombi formation
  2. INCREASED PT/PTT - All coagulation factors are being used up for platelet fragment thrombus formation
  3. DECREASED FIBRINOGEN - Fibrinogen linker molecule is consumed with massive thrombi formation
  4. ELEVATED D-DIMER - Elevated fibrin split products as a result of activation of FIBRINOLYSIS as well as CLOTTING
55
Q

What cell type can be visualized in a bone smear of DIC?

A

Schistocytes due to MICROANGIOPATHIC HEMOLYTIC ANEMIA

56
Q

What is the best screening test for DIC?

A

ELEVATED D-DIMER TEST
D-Dimer = Fibrin split products

The final step of clot formation is to actually lyse the clot and the fibrinogen that holds the plug together

57
Q

What are the 3 actions of PLASMIN?

A

1) Cleaves and inactivates FIBRIN (currently existing clot) + FIBRINOGEN (prevents future clots)
2) Cleaves and inactivates COAGULATION FACTORS
3) Blocks platelet AGGREGATION

58
Q

Name 2 etiologies of HYPERACTIVE PLASMIN (Disorders of fibrinolysis).

A

1) RADICAL PROSTATECTOMY: Release of UROKINASE activates plasmin
2) LIVER CIRRHOSIS: Reduced production of hepatic ALPHA2-ANTIPLASMIN -> Overactive plasmin

59
Q

DIC and HYPERACTIVE PLASMIN have very similar clinical presentations. How do you differentiate between the two?

A

1) DIC = ELEVATED D-DIMER (i.e. FIBRIN split product - To lyse clots of platelet and fibrin)
HYPERACTIVE PLASMIN = NO elevation in D-Dimer (NO CLOT containing fibrin TO LYSE, simply hyperactive plasmin), ELEVATED FIBRINOGEN split products
2) DIC - THROMBOCYTOPENIA (Consumption of PLT microthrombi)
HYPERACTIVE PLASMIN - NORMAL PLT Ct (No extra clot formation)

BOTH have INCREASED bleeding time (blocking PLT aggregation), INCREASED PT/PTT (Blocking coagulation factors), DECREASED fibrinogen (inactivating cleavage of serum fibrinogen)

60
Q

What is a D-DIMER?

A

FIBRIN SPLIT PRODUCT

61
Q

What is the difference in pathophysiology of DIC and HYPERACTIVE PLASMIN DISORDER?

A

DIC - CONSUMPTION of platelets/coagulation factors to form MICROTHROMBI and lots of CLOTS -> LOTS OF FIBRIN -> LOTS OF D-DIMER (fibrin split products)

HYPERACTIVE PLASMIN - No actual clot formation, just hyperactive plasmin -> CLEAVES LOTS OF SERUM FIBRINOGEN

62
Q

What is the treatment of overactive plasmin disorder?

A

AMINOCAPROIC ACID - Blocks activation of plasminogen

63
Q

HEMARTHROSES

A

Bleeding of the joints - seen in disorders of 2 hemostasis (e.g. HEMOPHILIA A)

64
Q

PETECHIAE, PURPURA, ECCHYMOSES measurements

A

PETECHIAE: =3mm

ECCHYMOSES >=1cm

65
Q

What is the normal PLT count and normal bleeding time?

A

PLT COUNT = 150-400K

BLEEDING TIME = 2-7min

STEP 6: HemeOnc PATHOMA (8 decks)

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