Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

USMLE Step I Pathology > Hemostasis and Related Disorders (Pathoma) > Flashcards

Hemostasis and Related Disorders (Pathoma) Flashcards

You may prefer our related Brainscape-certified flashcards:
USMLE® Step 1 flashcards
1
Q

Primary Hemostasis

A

Disruption of vessel wall.

  1. Blood vessel constricts - mediated by neural reflex and *endothelium (substance released from endothelial cell.
  2. Adhesion - vWf (from platelet itself and *endothelial cells –> Weibel-Palade body contain alpha granules made up of vWf and p-selectin) binds to exposed collagen. Platelets bind vWF using Gp1b.
  3. Aggregation - Platelet adhesion causes degranulation and the release ADP (dense granules) and TXA2. ADP induces platelets to express GP2b3a which facilitates aggregation. TXA2 allows for futher aggregation via linker molecule fibrinogen.

Results in formation of platelet plug.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Clinical features of primary hemostasis pathology

A

Mucosal and Skin bleeding

Mucosal - Epistaxis, hemoptysis, GI bleeding, hematuria, and menorrhagia

Intracranial bleeding occurs w/ severe thrombocytopenia.

Skin bleeding - petechiae, purpura, ecchymoses, brusing.

Petichiae are a sign of thrombocytopenia and are not usually seen in qualitative disorders.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Useful laboratory studies

A

Platelet count

Bleeding time

Blood smear

Bone marrow biopsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

ITP (Idiopathic Thrombocytopenic Purpura)

A

AI production of IgG vs. platelet antigens (i.e. GPIIb/IIIa

**MCC of thrombocytopenia in children and adults

Autoantibodies are producd by plasma cells in spleen. Antibody bound platelets are consumed by splenic macrophages –> thrombocytopenia.

Acute form arises in children –> weeks after viral infection or immunization. Self limited w/ in weeks of presentation

Chronic form arises in adults –> usually middle aged women. May be primary or secondary to SLE*. May cause short-lived thrombocytopenia in offspring; anti-platelet IgG can cross the placenta.

Lab findings:
low platelets; normal PT/PTT; Increase megakaryoctyes on bone marrow biopsy

Rx: Corticosteroids. (children respond well; adults relapse). IVIG in symptomatic bleeding (spleen eats IVIG instead of platelets –> effect is short lived.)

Splenectomy eliminates primary source of antibody and site of destruction. Only in refractory cases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Microangiopathic hemolytic anemia

A

Pathologic formation of platelet microthrombi in small vessels. As RBC crosses microthrombi –> lyses RBC –> schistocyte and hemolytic anemia.

Platelets are consumed in formation of microthrombi.

Classically seen in TTP and HUS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Thrombotic Thrombocytopenic Purpura (TTP)

A

Microthrombi due to decreased ADAMSTS13 which is needed to degrade vWf –> large multimers of vWf –> abnormal platelet adhesion.

Due to genetic defect or autoantibodi destruction (MC).

MC seen in adult female.

Clinical findings:

  • Skin and mucosal bleedings
  • Microangiopathic hemolytic anemia
  • Fever
  • Renal insufficiency
  • CNS abnormalities (predominant in TTP)

Lab findings:

  • Thrombocytopenia and increased bleeding time
  • Normal PT/PTT
  • Anemia w/ schistocytes
  • Increased megakaryocytes in bone marrow

Rx: Plasmapheresis and corticosteroids (esp. in TTP).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Hemolytic Uremic Syndrome

A

Due to endothelial damage by drugs or infection.

Ecoli O157:H7 infection releases verotoxin (Shiga-like toxin) –> damages endothelial cells (esp. in kidney and brain) –> microthrombi –> microangiopathic hemolytic anemia.

Classically seen in children w/ dysentery from undercooked beef.

Clinical findings:

  • Skin and mucosal bleedings
  • Microangiopathic hemolytic anemia
  • Fever
  • Renal insufficiency (predominant in HUS)
  • CNS abnormalities

Lab findings:

  • Thrombocytopenia and increased bleeding time
  • Normal PT/PTT
  • Anemia w/ schistocytes
  • Increased megakaryocytes in bone marrow

Rx: Plasmapheresis and corticosteroids (esp. in TTP).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Bernard-Soulier Syndrome

A

Genetic GP1b deficiency; platelet adhesion is impaired

Blood smear shows mild thrombocytopenia (increased destruction due to mutated receptor) w/ enlarged platelets (young platelets).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Glanzmann thombasthenia

A

Genetic GIIb/IIIa deficiency; platelet aggregation is impaired.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Aspirin Use

A

ASA irreversibly inactivates cyclooxygenase –> lack of TXA2 –> impaired aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Uremia

A

Uremia disrupts platelt function by creating both adhesion and aggregation problems.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Secondary Hemostasis

A

Goal is to stabilized primary platelet plug by making thombin to convert fibrinogen to fibrin.

Factors produced in liver in inactive state.

Activation requires:

  1. Exposure to an activating surface
  2. Phospholipid
  3. Ca++ (from dense granules)

Disorders are due to factor abnomalities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Clinical features of disorders of secondary hemostasis

A

Deep tissue bleeding into muscles and joints (hemarthrosis)

Rebleeding after surgical procedures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

PT

A

Measures extrinsic and common pathway

Measures Coumadin better

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

PTT

A

Measures intrinsic and common pathways.

Measures Heparin better

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Hemophilia A (8)

A

Genetic Factor VIII deficiency

X-linked recessive (predominately affects males)

Can arise from a new mutation w/o family hx

Presents w/ deep tissue, joint, and postsurgical bleeding. Severity depends on degree of deficiency.

Lab findings:

  • increased PTT and normal PT
  • decreased factor VIII
  • Normal platelet and bleeding time

Rx: Factor VIII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Hemophilia B

A

Genetic Factor IX deficiency

Resembles hemophilia A, except F IX levels decreased instead of F VIII.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Coagulation factor inhibitor

A

Acquired antibody against coagulation factor resulting in impaired factor funciton.

MC vs. VIII

Clinical and lab findings are similar to hemophilia A.

***Key is PTT doesn’t correct w/ mixing normal plasma w/ patient’s plasma (mixing study) due to inhibitor. PTT does correct in hemophilia A.

19
Q

Von Willebrand Disease

A

*MC inherited coagulation disorder.

Genetic vWF deficiency

Cause quantitative or qualitative deficiency

MC type is auto dominant w/ decreased vWF levels.

Presents w/ mild mucosal and skin bleeding (due to decreased platelet adhesion)

Labs:

  • Increased bleeding time
  • Increased PTT(need vWF to stabilize factor VIII*) normal PT
  • *Abnormal ristocetin test (ristocetin doesn’t cause platelet aggregatoion)

Rx: *Desmopressin –> increases vWF release from Weibel-Palade bodies

20
Q

Vitamin K defiency

A

Disrupts function of gamma-carboxylation of factors (2,7,9,10 C and S).

Deficiency occurs in:

  • Newborns (lack of gut flora)
  • Long-term abx therapy (kill gut flora)
  • Malabsorbtion (fat soluble)
21
Q

Liver failure

A

Decreased production of coag factors

Decreased activation of vitamin K by epoxide reductase

Effect of liver failure on coagulation is followed using PT

22
Q

Large-volume transfusion

A

Dilutes coagulation factors

Results in relative deficiency.

23
Q

Heparin-Induced-Thrombocytopenia (HIT)

A

Platelet destruction that arises secondary to heparin therapy. Heparin binds to Platelet Factor 4 –> autoantibodies.

Fragments of destroyed platelets may activate remaining platelets, leading to thrombosis.

Don’t give these patients Warfarin when taking of Heparin –> increased risk for skin necrosis

24
Q

Disseminated Intravascular Coagulation

A

Pathologic activation of coagulation cascade

Widespread microthrombi result in ischemia and infarction

Consumption of platelets and factors results in bleeding, especially IV sites and mucosal surface.

Almost always secondary to another disease process:

  • Obstetric complication (placenta includes thromboplastin –> DIC)
  • Sepsis (endotoxin and macrophage cytokines activate cascade)
  • Adenocarcinoma (mucin activates cascade)
  • Acute Promyelocytic Leukemia
  • Rattlesnake bite (venom)

Lab findings:

  • decreased platelet count
  • PT/PTT increased
  • Decreased fibrinogen
  • Microangiopathic hemolytic anemia
  • Elevated fibrin split products (D-dimer) –> best screening test

Rx: Address underlying cause. Transfuse blood products and cryoprecipitate as needed.

25
Q

Plasmin actions

A

Activated by tPa

Shut off by alpha-2 anti-plasmin

3 jobs:

  1. Cleaves fibrin and fibrinogen
  2. Destroys coag factors
  3. Blocks platelet aggregation.

Disorders result from plasmin overactivity.

26
Q

Radical prostatectomy fibrinolysis

A

Release of urokinase –> activates plasmin

*Presentation resembles DIC

Labs:

  • Increased PT/PTT
  • Increased bleeding time w/ *normal platelet count
  • Increased fibrinogen split products, but No d-dimers w/

Rx; Aminocaproic acid: blocks activation of plasminogen

27
Q

Cirrhosis related fibrinolysis

A

Reduced production of alpha-2-antiplasmin

*Presentation resembles DIC

Labs:

  • Increased PT/PTT
  • Increased bleeding time w/ *normal platelet count
  • Increased fibrinogen split products, but No d-dimers w/

Rx; Aminocaproic acid: blocks activation of plasminogen

28
Q

Characterstics of thrombus

A
  1. Lines of Zahn (layers of RBCs and platelet fibrin)
  2. Attachment to vessel wall

Both features distinguish thrombus from postmortem clot.

29
Q

Risk factors for thrombosis

A

Virchow’s Triad:

  • Stasis or turbulent flow (i.e. immobilization, cardiac wall dysfunction, aneurysm)
  • Endothelial damage (exposed collagen, no PGI2 or NO produced, no heparin like molecules secreted, no tPA production, and no thrombomodulin.) Caused by atherosclerosis, vasculitis, and high levels of homocysteine (secondary to B12 or folate deficiency or cystathionine beta synthase)
  • Hypercoaguable state (classically present w/ recurrent DVTs or DVTs at a young age)
30
Q

Homocystinuria

A

Deficiency in cystathionine beta synthase

Results in high homocysteine levels w/ homocystinuria.

Characterized by vessel thrombosis, mental retardation, lens dislocation, and long slender fingers.

31
Q

Protein C and S defiency

A

Decreases negative feedback on coagulation cascade

Protein C and S normally inactivate factors V and VIII

Increased risk for Warfarin skin necrosis

32
Q

Warfarin skin necrosis

A

Warfarin blocks gamma carboxylation of factors 2,7,9,10,C, and S.

First factors gone are C and S.

Increased risk for thrombus early –> heparin bridge.

If deficient in C and S –> very increased risk for hypercoaguable state and skin thrombi –> warfarin skin necrosis.

33
Q

Factor V Leiden

A

Mutated form of factor V that lacks cleavage site for deactivation by proteins C and S.

MC inherited cause of hypercoaguable state.

34
Q

Prothrombin 20210A

A

Inhertited point mutation in prothrombin

Results in increased gene epression.

Promotes thrombus formation

35
Q

ATIII deficiency

A

Decreases protective effects of heparin-like-molecules produced by endothelium. Increasing the risk for thrombus.

PTT does not rise w/ standard heparin dosing.

High doses of heparin activate limited ATIII; Warfarin is then given to maintain anticoagulated state.

36
Q

OCP

A

Associated w/ hypercoaguable state due to estrogen increasing production of coag factors.

Increases the risk for thrombosis.

37
Q

Thromboembolus

A

MCC of embolus (95%)

38
Q

Atherosclerotic embolus

A

Due to plaque that dislodges.

Characterized by the presence of cholesterol clefts in the embolus.

39
Q

Fat embolus

A

Associated w/ bone fractures, particularly long bones and soft tissue trauma

Develops while fracture is still present or shortly after repair

Dyspnea and peteciae on the skin overlying chest.

40
Q

Gas embolus

A

Seen in decompression sickness

Presents w/ joint and muscle (bends) pain and respiratory sx (chokes)

Chronic form (Caisson disease) characterized by multifocal ischemic necrosis of bone.

May also occur during laparoscopic surgery –> air pumped into the abdomen enters blood stream.

41
Q

Amniotic fluid embolus

A

Amniotic fluid enters circulation during labor or delivery.

Presents w/ shortness of breath, neurologic sx, and DIC (from tissue thromboplastin in embryonic fluid)

Characterized by squamous cells and keratin debris from fetal skin in embolus

42
Q

PE

A

Usually due to thromboembolus from femoral, ileach, or popliteal veins.

Most ofen is clinically silent.

Lung tissue has dual blood supply and emboli are usually small.

Pulmonary infarction possible if large or medium sized artery w/ pre-existing cardiopulmonary compromise.

Only 10% of PEs present w/ pulmonary infarction.

Clinical featurs:

  • SOB, hemoptysis, pleuritic chest pain, and pleural effusion.
  • V/Q scan shows mismatch
  • Spiral CT shows a vascular filling defect
  • Lower extremity doppler US detects DVT
  • D-dimer is elevated

Gross exam reveals hemorrhagic (second blood supply and loose tissue) wedge-shaped infarct

Sudden death if large saddle embolus due to electromechanical dissociation of heart.

Pulmonary HTN in pts w/ chronic emboli that are reorganized

43
Q

Systemic embolism

A

Usually due to thromboembolus.

MC arise in left heart.

Travel down systemic circulation to occlude flow to organs; MC the lower extremities.

USMLE Step I Pathology (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions