platelet and coagulation disorders I & II - Zaloga Flashcards

1
Q

what is the most common cause of mild bleeding diathesis?

A

-von willebrand disease and aspirin use

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2
Q

hemophilias

A

-clotting factors aren’t working –> severe, deeper bleeding

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3
Q

defects of small vessels

A
  • present with purpura (hemorrhage into skin) or ecchymoses (bruises)
  • hematoma is extravasated blood that creates a mass
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4
Q

defects of primary hemostasis (platelet plug)

A
  • due to platelets or von willebrand disease

- present with small bleeds in skin or mucosa –> petechia, epistaxis, GI, menorrhagia

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5
Q

defects of secondary hemostasis (coagulation)

A
  • bleeds into soft tissues (muscles/joints)
  • hemarthrosis (bleeding into joints)

cardiovascular collapse and shock if mechanisms cannot keep up with blood loss –> organ failure

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6
Q

lab tests for evaluating hemorrhagic diathesis

A
  1. prolonged PT or PTT
  2. platelet counts
  3. tests for platelet function: aggregate in response to thrombin
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7
Q

bleeding disorder from vessel wall abnormalities

A
  • often have petechia and purpura
  • platelet count, PT, PTT normal (only vessel wall is dysfunctional)

cause:
1. infections causing vasculitis; DIC
2. drug rxns leading to hypersensitivity of vessels
3. scurvy and Ehlers-danlos –> collagen defects
4. Henoch-Schönlein purpura –> activate compliment causing vessel damage
5. Perivascular amyloidosis –> build up of amyloid light chain within plasma
6. Hereditary hemorrhagic telangiectasia (aka Weber-Osler-Rendu syndrome) –> dilated, tortuous vessels leading to severe bleeding

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8
Q

bleeding disorders from platelet # - thrombocytopenia

-quantitative effects

A
  • <100,000 is thrombocytpenia
  • worry about spontaneous nontraumatic intracranial bleeding when platelet count <20,000; bleeding also in skin (petechia) and mucous membranes (GI;GU)
  • normal PT/PTT

causes of thrombocytopenia:

  1. decreased platelet production (ex. marrow suppression, MDS)
  2. decreased platelet survival (ex. ITP, alloantibodies, DIC, thrombotic microangiopathies)
  3. sequestration: splenomegaly
  4. dilution: massive transfusions
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9
Q

bleeding disorders due to platelet dysfunctions

-qualitative effects

A

-inherited or acquired –> normal platelet count, but not function

inherited disorders:

  1. Bernard-Soulier Syndrome: deficiency of GP1b-9 –> defective adhesion of platelets
  2. Glanzmann Thrombasthenia: deficiency of GP2b/3a –> defective platelet aggregation (cannot bind fibrinogen in response to ADP)
  3. disorders of platelet secretion (storage pool disorder): mediators not released from granules during platelet activation (do not recruit other platelets)

acquired disorders:

  1. aspirin and NSAIDs: inhibits COX which makes TXA2 for platelet aggregation
  2. uremia: defects in adhesion, aggregation, and granule secretion
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10
Q

immune thrombocytopenic purpura

A
  • IgG against the platelet antigens (GP2b/3a or GP1b-9)**
  • adults: due to autoimmune (SLE) or lymphocyte abnormality, chronic ITP, has viral prodrome
  • child: develop acute ITP that trigger autoantibodies and is usually viral
  • thrombocytopenia improved with splenectomy (not producing antibodies)
  • primary ITP –> no symptoms, only petechia and purpura
  • chronic ITP –> thrombocytopenia, low platelets, increased megakaryocytes (need to make more thrombocytes so it makes immature cells), normal PT/PTT
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11
Q

microangiopathic hemolytic anemia (MAHA)

A
  • excessive activation of platelets leads to coagulation in small vessels –> schistocytes***
  • see in TTP and HUS**
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12
Q

thrombotic thrombocytopenic purpura (TTP)

A
  • decreased ADAMTS13 enzyme –> cannot degrade vWF into monomers –> abnormal platelet adhesion/aggregation forming micro thrombi –> organ dysfunction
  • leads to thrombocytopenia (platelets used up) and MAHA (schistocytes)
  • due to autoantibody (inhibits metalloprotease) or inherited mutation
  • pentad of fever, kidney problems, NEURO defects***
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13
Q

hemolytic uremic syndrome (HUS)

A
  • infection of E. coli 0157:H7 –> release verotoxin (shiga like toxin) –> damage endothelial cells and activate platelets –> producing micro thrombi –> organ dysfunction
  • normal levels of ADAMTS13
  • bloody diarrhea and irreversible RENAL damage**
  • no CNS symptoms
  • see MAHA and thrombocytopenia

atypical HUS: defects in compliment regulatory proteins (ex. factor H, CD46, factor I) –> platelets susceptible to compliment activation –> thrombocytopenia**
-due to inherited mutations or acquired autoantibodies

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14
Q

DIC and thrombotic microangiopathies**

A
  • similarities: microvascular occlusion and MAHA

- differences: no coagulation cascade activation in HUS or TTP (PT and PTT normal)**, but there is activation in DIC

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15
Q

drug induced thrombocytopenia

A
  • decreases platelet count
  • heparin forms complex with platelet factor 4 (PF4) on the surface of platelets –> IgG autoantibodies against complex bind to platelet Fc receptor (opsonized) –> consumed by macrophages in spleen –> thrombocytopenia
  • platelet fragments in circulation –> activate remaining platelets –> thrombosis (dangerous)
  • main drug used is heparin - HIT***

other drugs: quinine, quinidine, vancomycin bind platelet GPs creating antigenic determinants recognized by antibodies

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16
Q

2 ways that thrombocytopenia occurs in heparin induced thrombocytopenia (HIT)

A
  1. type I: thrombocytopenia occurs rapidly after therapy –> direct effect of heparin on platelet activation
  2. type II: thrombocytopenia less common, antibodies formed days after therapy (type 4 cell mediated) –> life threatening venous and arterial thrombosis
17
Q

role of fibrin

A
  • made in secondary hemostasis by coagulation factors to stabilize the platelet plug
  • factor 13 cross-links fibrin
18
Q

hemorrhagic diathesis due to clotting factor deficiency

A

-bleeding into soft tissues (muscle and joints, cranial cavity)

hereditary deficiency –> single clotting factors

  • Hemophilia A (factor 8)
  • Hemophilia B (factor 9)

acquired deficiency –> multiple clotting factors

  • vit.K (factors 2,7,9,10, protein C)
  • liver disease (prothrombin, thrombin, protein S, many coagulation factors)
  • DIC (bleeding and thrombosis at same time)
19
Q

vWF**

A
  • stabilized factor 8** (needed to help factor 9 convert factor 10 to 10a)
  • deficient factor 8 with vWF disease and hemophilia A
  • made in endothelial cells and platelets
  • adhesion/aggregation of platelets after binding to collagen and GP1b
20
Q

von willebrand disease

A
  • most common inherited bleeding disorder (autosomal dominant)
  • decreased factor 8 and increased PTT**
Type1: mild vWF deficiency --> mild bleeding 
Type 3 (autosomal recessive): severe vWF deficiency --> sever bleeding 

Type 2: normal levels of vWF but multimers are not active –> no platelet binding –> mild bleeding

21
Q

hemophilia A

A
  • factor 8 deficiency**
  • X-linked recessive
  • mutations causing qualitative and quantitative problems
  • very low levels before symptoms occur –> bruising, hemorrhage after trauma and in joints, no petechia
  • prolonged PTT, normal PT**
22
Q

hemophilia B - Christmas disease

A
  • factor 9 deficiency**
  • X-linked recessive
  • same labs/clinical finding as hemophilia A
23
Q

disseminated intravascular coagulation (DIC)

A
  • secondary to other disorders*
  • excessive activation of coagulation cascade –> thrombi–> ischemia, infarction, MAHA**
  • after consumption of platelets/factors –> severe bleeding**
  • clotting occurs with exposure to TF –> binds factor 7 to activate factor 10a and 9
24
Q

role of thrombin

A
  • platelet aggregation
  • convert fibrinogen to fibrin
  • activate factor 13, 11, 5**
25
Q

what inhibits spontaneous coagulation leading to fibrinolysis?

A
  • thrombomodulin (normal endothelium) binds to thrombin in the blood –> activates protein C –> inactivates factors 5a and 8a
  • plasmin also in blood
26
Q

2 mechanisms that trigger DIC

A
  • release tissue factor and other procoagulants into circulation
  • seen with trauma, OB, malignant neoplasms, sepsis, endothelial injury**
  • need a lot of transfusions
  • tissue factor from placenta (OB), trauma, or burns
  • mucus from adenocarcinoma –> activate factor 10
  • endothelial injury –> platelet activation/coagulation; TNF is a mediator
  • acute DIC –> OB, trauma –> bleeding tendency
  • chronic DIC –> cancer –> thrombotic tendency
27
Q

role of TNF in inflammatory rxn that damages endothelial cells

A
  • induce endothelial cells to express tissue factor and adhesion molecules
  • decrease expression of thrombomodulin
28
Q

complications of blood transfusions

A
  1. febrile nonhemolytic rxn (most common)
    - fever and chills after 6 hours
    - cause: inflammatory mediators from donor leukocytes
    - decreased by limiting donor leukocyte contamination with filters
    - treat: antipyretic
29
Q

complications of blood transfusions

A
  1. urticarial allergic rxns (hives)
    - triggered by allergen in donor recognized by IgE antibodies in recipient
    - treat: antihistamines
30
Q

complications of blood transfusions

A
  1. allergic rxns
    - blood products containing antigens given to recipient who is sensitized
    - IgA deficiency patients** (recognized by IgG in recipient)
31
Q

complications of blood transfusions

A
  1. hemolytic rxns
    - ACUTE hemolytic rxns: preformed high affinity IgM antibodies against blood group antigens A and B –> induce compliment mediated intravascular hemolysis
    - DIRECT Coombs test + if not all RBCs are lysed
  • CHRONIC hemolytic rxns: IgG antibody recognized RBC antigens (Rh, Kell, Kidd) already sensitized to from previous blood transfusion –> activates compliment –> intravascular hemolysis
  • other antibodies opsonize –> extravascular hemolysis in spleen
  • INDIRECT Coombs test +, low haptoglobin
32
Q

complications of blood transfusions

A
  1. transfusion related acute lung injury (TRALI)
    - priming event (pre-existing lung disease) sensitizes patient to neutrophils in microvasculature –> transfusion activates the neutrophils with foreign HLA antigen that are recognized by donor antibodies –> inflammatory rxn
    - more likely in transfusions with high donor antibodies like frozen plasma and platelets
    - cause respiratory failure
    - avoid plasma from females
    - only get plasma from males or never plasma females (check anti-HLA antibodies 1st)
33
Q

complications of blood transfusions

A
  1. infections
    - due to bacterial or viral infections in donated blood
    - bacteria caused by skin flora (grows in platelet preps better)
    - cause fever, chills, hypotension
    - start broad spectrum antibiotics
    - donor screening to decrease viral transmission