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Coagulation Flashcards

1
Q

Primary hemostasis: name the membrane receptor, Adhesive protein, and appropriate surface

A

Membrane receptor: Glycoprotein 1b

Adhesive protein: Von Willebrand factor

Appropriate surface: Subendothelial matrix (collagen)

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2
Q

name the events that occur during platelet activation:

A
  • platelets are activated by binding to vWF

Secretion – alpha-granules and dense bodies (2nd messengers)

  • Activation of GP IIb/IIIa receptor
  • Shape change – from rounded discs to flat plates
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3
Q

what protein is responsible for holding platelets together during aggregation?

A

fibrinogen

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4
Q

what steps occur during secondary hemostasis?

A

Secondary hemostasis = fibrin clot formation

Formation of thrombin

Formation of fibrin clot
- with crosslinking of fibrin monomers by Factor XIIIa

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5
Q

what molecules will inhibit secondary hemostasis?

A

Serine protease inhibitors (antithrombin)

Protein C pathway (controls Va and VIIIa)

Fibrinolytic system (removes excess clot- TPA)

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6
Q

what are the components of Anti-thrombin?

A

Serine Protease

+

SERPIN

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7
Q

Serine protease + SERPIN forms what?

A

Enzyme-Inhibitor Complex

(antithrombin

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8
Q

what molecules does serine protease (antithrombin) inhibit?

A

Thrombin

factors IXa, Xa, XIa, and XIIa

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9
Q

Activated Protein C (APC) plus Protein S serve to inactivate cofactors __________

A

Va and VIIIa

the major Cofactors in coagulation cascade

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10
Q

Protein C or Protein S deficiencies result in _________________

A

hypercoaguable states

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11
Q

what are the effects of a Factor V Leiden mutation?

A

promotes coagulation

resistance to enzymatic inactivation by the Protein C/S complex

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12
Q

In the presence of fibrin, _________________ can bind to plasminogen and convert it to an active enzyme, plasmin

A

tissue plasminogen activator (TPA)

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13
Q

Plasmin breaks down previously cross-linked fibrin monomers into what?

A

fibrin degradation products (FDP)

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14
Q

Uncontrolled activation of plasmin can result in bleeding complications as ____________ and _____________

A

fibrinolysis and fibrin(ogen)olysis

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15
Q

___________ inhibits serine proteases

A

antithrombin

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16
Q

protein C inhibits ________

A

cofactors Va and VIIIa

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17
Q

what are the screening tests of hemostasis?

A

Prothrombin Time (PT)
Partial Thromboplastin Time (PTT)
Platelet count
Bleeding time (BT)/PFA-100

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18
Q

The most important part of defining the cause of a bleeding disorder is _______________

A

a careful clinical history

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19
Q

Prothrombin Time (PT) screens for activity of proteins in the __________ pathway

A

extrinsic

factors V, VII, II, X and fibrinogen

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20
Q

Partial thromboplastin time (PTT) screens for activity within the _________ pathway

A

intrinsic

factors XII, XI, IX, VIII… X, V, II and fibrinogen

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21
Q

what is the normal range for platelet counts?

A

normal range is generally 150,000 to 400,000/µL

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22
Q

what is thrombocytopenia? thrombocytosis? thrombocythemia?

A
  • thrombocytopenia refers to a decrease in platelet number

- thrombocytosis and thrombocythemia denote an increase in platelet number

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23
Q

what do the results of a positive mixing test show? what about a negative test?

A
  • If the mixing study corrects the clotting time, a deficiency of some factor(s) is felt to be present
  • If the mixing study does not correct the clotting time, an inhibitor is felt to be present, either factor-specific or lupus anticoagulant type
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24
Q

how are bleeding disorders classified?

A

Congenital vs. Acquired
Mild vs. Severe
Primary vs. Secondary Hemostasis
Regulatory Disorder

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25
what are the CLINICAL manifestations of Disorders of Primary Hemostasis ?
``` Mucocutaneous bleeding (vWF disease) Excessive bleeding with trauma (vWF-d, Hemophilia A &B) ```
26
what are the lab findings of Disorders of Primary Hemostasis ?
- Prolonged BT/PFA-100 | - Thrombocytopenia
27
what are the clinical manifestations of Disorders of secondary Hemostasis ?
- Soft tissue bleeding | - Excessive bleeding with trauma
28
what are the lab findings of Disorders of secondary Hemostasis ?
Prolonged PT and PTT Prolonged TT (thrombin time)
29
what are the clinical manifestations of regulatory disorders of Hemostasis ?
Soft tissue bleeding Excessive bleeding with trauma
30
what are the lab findings of regulatory disorders of Hemostasis ?
Normal PT and PTT Normal bleeding time Normal platelet count
31
list the characteristics of von Willebrand disease:
Autosomal dominant disorder (usually) Due to abnormalities of vWF Abnormality may be quantitative, qualitative or both Mucocutaneous bleeding is the dominant clinical manifestation
32
what is the Factor VIII Complex?
vWF + factor VIII procoagulant
33
what is the most commonly inherited bleeding disorder?
von Willebrand disease - effects 1% of population
34
what are the 3 classes/types of von Willebrand disease?
Type 1: Quantitative deficiency (partial) Type 2: Qualitative deficiency Type 3: Quantitative deficiency (total)
35
clinical manifestations of von Willebrand disease:
``` *mucosal bleeding (NOT SEEN in hemophilia A) Epistaxis (nosebleeds) Ecchymoses (>1cm bruises) Bleeding with trauma or surgery Symptoms improve after adolescence ```
36
in a patient with vWD, what lab tests would be normal? which would be elevated/prolonged? which would decrease?
PT & platelet count = normal ``` BT/PFA-100: Prolonged *PTT: prolonged *VIII: Decreased vWF:ag: Decreased vWF:Rcof: Decreased ```
37
treatments for vWD include what?
Desmopressin Antifibrinolytic agents Factor VIII concentrates Cryoprecipitate
38
list the general characteristics of Hemophilia A:
Sex-linked recessive disorder Deficiency of factor VIII Recurrent soft tissue bleeding Symptoms usually start in early childhood
39
clinical characteristics of Hemophilia A:
``` Hemarthrosis Soft tissue bleeding Excessive bleeding with trauma Intramuscular hematomas Intracerebral hemorrhage Bleeding into other tissues ```
40
which lab tests are ABNORMAL for Hemophilia A? (include wether they are prolonged or decreased)
PTT: Prolonged Factor VIII: Decreased (PT time is normal- no effect on extrinsic clotting)
41
what is "Severe" hemophilia A? what is its characteristics?
<1% factor VIII Recurrent spontaneous soft tissue and joint space bleeding
42
what are the characteristics of moderate and mild Hemophilia A?
Moderate: 1 - 5% factor VIII Bleeding with minor trauma Minor: >5% factor VIII Bleeding with major trauma
43
what treatments are used for Hemophilia A?
Factor VIII Concentrates Fibrinolytic inhibitors
44
list the disease related complications of Hemophilia A:
Arthritis and joint destruction Pseudotumors Intracranial bleeding Retroperitoneal bleeding
45
list the treatment related complications of Hemophilia A:
Antibodies to factor VIII | Infectious diseases
46
list the characteristics of Hemophilia B:
- Sex-linked, recessive disorder - Deficiency of factor IX (INTRINSIC pathway) - Clinical and laboratory presentation similar to deficiency of factor VIII Mild, moderate, severe deficiencies are seen Mild cases may be difficult to recognize clinically
47
list the disease related complications of Hemophilia B:
SAME AS HEMOPHILIA A Arthritis and joint destruction Pseudotumors Intracranial bleeding Retroperitoneal bleeding
48
list the treatment related complications of Hemophilia B:
Antibodies to factor IX | Infectious diseases
49
what are the mechanisms for thrombocytopenia?
Decreased platelet production Increased destruction Sequestration Congenital versus acquired
50
list the clinical characteristics of Acute/childhood ITP | ITP = immune thrombocytopenia purpura
``` Viral prodrome (early symptom) common Sudden onset Severe thrombocytopenia Frequently undergoes spontaneous remission M:F close to 1:1 ```
51
list the clinical characteristics of Adult/chronic TTP | TTP = thrombotic thrombocytopenia purpura
``` No antecedent infection Gradual onset Moderate thrombocytopenia Infrequent spontaneous remission More common in females ```
52
what are the clinical characteristics of all ITP's?
Petechiae Ecchymoses (bruising) Bleeding with trauma or surgery
53
what is the pathophysiology for ITP?
- Autoantibodies directed at the platelet membrane antigens - GPIb/IX and IIb/IIIa common targets - Increased IgG bound to the platelet surface promotes increased sequestration/destruction by the reticuloendothelial system
54
what changes in the blood and bone marrow can be seen during ITP?
Megakaryocytes normal to increased No microangiopathic changes on blood smear review
55
Therapy for ITP includes:
Corticosteroids Intravenous immunoglobulin Immunosuppression Splenectomy
56
what is Thrombotic Thrombocytopenic Purpura (TTP)?
- Acute disorder characterized by intravascular platelet activation with formation of platelet-rich microthrombi throughout the circulation - Left untreated, TTP is associated with high mortality.
57
TTP is Now known to be caused by a deficiency of ____________, a metalloproteinase
ADAMTS 13
58
what does the ADAMTS 13 metalloproteinase do?
degrades very-high-molecular-weight vWF
59
what lab method is used to detect TTP?
HUS-TTP spectrum
60
what is Disseminated Intravascular Coagulation (DIC)?
Unregulated, widespread intravascular activation of the hemostatic system Systemic formation of thrombin and plasmin with consumption of clotting factors and bleeding
61
the result of DIC is the formation of what 2 conditions?
- microvascular thrombosis | - hemorrhaging
62
what can cause DIC?
Infections (gram negative sepsis) Tissue injury (trauma, burn, surgery) Obstetrical complications Certain malignancies
63
list all the clinical signs of DIC:
``` Bleeding from multiple sites Thromboembolic problems Hypotension and shock Respiratory dysfunction Hepatic dysfunction Renal dysfunction CNS dysfunction ```
64
During therapy for DIC, what blood products can be transfused?
FFP: coagulation & regulatory proteins Cryo: fibrinogen, VIII, vWF Platelets: platelets
65
heparin works in the same way as what enzyme/Factor in the coagulation cascade?
antithrombin

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