8/20- Acquired Bleeding Disorders Flashcards Preview

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Flashcards in 8/20- Acquired Bleeding Disorders Deck (33):
1

What are the 3 most common causes of acquired bleeding disorders? Others?

- DIC

- Liver failure

- Vitamin K deficiency

Also:

- Factor specific inhibitor

- Trauma

- Dilutional coagulopathy

2

Type of bleeding varies with etiology

- What symptoms/type of bleeding are common in platelet defects (thrombocytopenia and function defect) and coagulopathy?

Platelet defects (thrombocytopenia and function defect):

- Petechiae characteristic

- Superficial bruising characteristic (small, multiple)

- Sometimes positive family Hx

- Rarely hemarthrosis and deep hematomas

Coagulopathy:

- Hemarthroses and deep hematomas are characteristic

- Superficial bruising is common (large, solitary)

- Family Hx is common

- Petechiae are rare 

A image thumb
3

Local vs. systemic bleeding (what do they suggest?)

- Single area suggests a structural defect

- Multiple sites suggest a systemic defect

4

PE of a bleeding patient involves what?

- Determine all sites of hemorrhage

- Determine presence of jaundice, hepatomegaly, splenomegaly, or telangiectasias

Platelet abnormalities, von Willebrand disease, vascular defects

- Mucocutaneous bleeding (nose bleed, menorrhagia)

- Petechiae

Coagulation factor defects

- Intramuscular or intra-articular bleeding

- Mucocutaneous bleeding (nose bleed, menorrhagia)

- No petechiae

5

What screening lab tests should be done on a bleeding pt?

- CBC (Hb,Hct, WBC, platelet count, WBC differential)

- PT, PTT, and fibrinogen

- Platelet function study

6

What are some acquired coagulation disorders? Inherited?

Acquired:

- DIC

- Liver disease

- Vitamin K deficiency

- Dilutional coagulopathy

- Trauma

- Factor specific inhibitor

Congenital:

- Hemophilia A

- Hemophilia B

- Von Willebrand disease

- Other

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7

Describe coagulation disorders in regard to liver disease

- Decreased synthesis of all clotting factors except factors VIII and XIII

- Decreased clearance of fibrin degradation products (= FSP) or D-dimer

- Thrombocytopenia (2o to congestive splenomegaly and decreased thrombopoietin)

- Increased fibrinolysis, low-grade DIC, vitamin K deficiency (with biliary disease and alcoholism)

8

What would key lab results be in liver disease?

- Prolonged PT and PTT

- Low fibrinogen level (fibrinogen synthesis often maintained except in liver failure)

- Low coagulation factor levels (commonly monitored by FV and FVII as surrogates for the liver)

- Factor VIII is not decreased

9

Management for bleeding risk due to liver disease?

Transfusion therapy:

Fresh frozen plasma (FFP)

- FFP contains all coagulation factors, VWF multimers, and fibrinolytic control proteins, as well as plasminogen and anticoagulants.

Cryoprecipitate: Fibrinogen (+ factor VIII, vWF, factor XIII, fibronectin)

Platelets

10

Case)

A 46 yo man with severe liver failure awaiting liver transplant

PT: 36.3 s, PTT: 48.5 s, fibrinogen 98 mg/dL

D-dimer 2.8 ug/mL (moderate positive)

Factor V 4%, factor VII 2%, factor VII 169%

Classic

11

What is DIC? What processes does it involve?

Disseminated Intravascular Coagulation

Coagulation activation leading to fibrin formation and consumption coagulopathy

- Fibrin formation induces thrombosis

- Consumption coagulopathy induces bleeding

No primary DIC! 

- It is always secondary to clinical conditions (can get bleeding and thrombosis at the same time)

12

What are some predisposing conditions for DIC?

Three most common causes:

- Infection: Gm- (endotoxin); sepsis

- Malignancy: acute promyelocytic leukemia (M3)- tissue factor in promyelocytes

- Obstetric complication: abruptio placenta, missed abortion, eclampsia, and amniotic fluid embolism

Other causes:

- Massive trauma

- Heat stroke

- Burns

- Extensive surgery

13

Pathophysiolog of DIC

Trigger of coagulation activation:

- Disturbance of endothelial cells

- Entry of tissue factor into circulation

- Circulating microvesicles

Fibrinolysis always present to a variable degree

- Fibrin and fibrinogen are degraded by plasmin

Fibrin degradation or split products (FDP or FSP) accumulate; these inhibit stable clot formation and platelet function -> bleeding

14

Diagnosis of DIC? Lab findings?

Based on clinical and laboratory findings. Patients must have a predisposing condition.

- DIC is always secondary. No primary DIC.

Typically, the bleeding is diffuse; e.g., a patient in the SICU who’s oozing blood from multiple sites, like IVs, arterial lines, tracheostomy, chest tube, Foley catheter, and other drains.

- Localized bleeding may be surgical bleeding

Labs:

- PT should be prolonged and D-dimer should be positive!!

- PTT may be prolonged but can be normal or even shortened (“Paradoxical shortening of PTT”); measure of FVIII which can be really increased?

- Platelet count may be decreased but can be normal or increased as platelet being an acute phase reactant.

- Fibrinogen may be decreased but can be normal or increased as an acute phase reactant.

- Schistocytes may be present on the peripheral blood smear.

15

What is shown here? 

Q image thumb

PBS with Schistocytes (fragmented RBCs)

16

What is included on the DIC panel?

- PT

- PTT

- Fibrinogen

- Thrombin time

- D-dimer

- Platelet count

17

(Positive) results of DIC panel?

- PT: elevated (consumption coagulopathy)

- PTT

- Fibrinogen

- Thrombin time

- D-dimer: elevated (hypercoagulable state)

- Platelet count

18

Differential diagnosis of DIC?

- Liver failure

- Dilutional coagulopathy

- TTP (thrombotic thrombocytopenic purpura)

- HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets in pregnancy)

- Extensive thrombosis

These can co-exist; clinical picture is important

19

Treatment of DIC?

1. Treat underlying cause

2. Supportive care (maintain BP, etc.)

3. Replacement therapy for bleeding (FFP, cryoprecipitate, and/or platelet transfusions)

4. Heparin (only when thrombosis dominant picture)

5. Antifibrinolytic agent (controversial)

20

What coagulation factors/other substances are affected by Vitamin K deficiency? Mechanism behind this?

- II, VII, IX, and X (2, 7, 9 and 10)

- Protein C and S

These are made in the liver and require gamma-carboxylation that requires vitamin K

- AA is essential for Ca binding, which mediates adherence of these clotting factors to phospholipid surfaces

- Vitamin K deficiency is associated with decreased activity of these factors and a hemorrhagic tendency

21

Describe gamma-carboxylation of prothrombin?

What will you see if this process is not working (measurable)?

- Vitamin K is a cofactor necessary for this process (gamma-carboxylation of prothrombin precursor)

- In its absence, precursor PIVKA could be detected in the serum/plasma 

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22

What are risk factors and major causes of Vitamin K deficiency?

(Surprisingly uncommon in the ICU)

Risk factors:

- Prolonged Abx therapy

- MRCP (mental retardation, cerebral palsy)

Major causes:

- Inadequate dietary intake

- Malabsoprtion

- Abx

- In newborns, severe deficiency causes hemorrhagic disease of the newborn (Vitamin K does not cross from mother to child?)

23

What are the lab findings in Vitamin K deficiency?

Prolonged PT and PTT

- PT tends to be prolonged earlier than PTT

Low factors II, VII, IX, and X (2, 7, 9 and 10)

- Factor VII has the shortest half life (5 hrs) among these

Low protein S and C

- Protein C has the shortest half life (3 hrs)

24

Diagnostic process of Vitamin K deficiency?

- In practice, Dx confirmed by correction of PT upon administering Vitain K 

- Msmt of FII, V, and VII (2, 5, and 7) (expect to see normal 5 and decreased 2 and 7)

- Msmt of PIVKA-II (protein induced by vitamin K absence)

25

Therapy for Vitamin K deficiency?

- Oral or parenteral vitamin K (takes 10-12 hrs); IV may cause anaphylactic reaction

For urgent reversal:

- FFP

- Prothrombin complex concentrate (contains FII, VII, IX, and X)

26

What causes dilutional coagulopathy?

Caused by massive transfusions with RBCs and fluid resuscitation

- RBCs do not contain coagulation factors and platelets

- Dilutional thrombocytopenia may also occur

- Fibrinogen level should be carefully monitored

27

What is spontaneously acquired factor specific inhibitor? Which is the most common?

Most common: FVIII inhibitor (8) 

- May be associated with autoimmune disorders

- Almost all cases are IgG, mostly IgG4

- Inactivation of FVIII is time-dependent

Less common: FV, FXI, or FXIII inhibitor (5, 11, 13)

Very rare: FIX inhibitor (9)

Of note: FVIII or FIX inhibitor associated with hemophilia A or B is not uncommon

28

Trauma can cause what in regards to clotting/platelets? Consequences?

Trauma can cause hyperfibrinolysis

- Unless corrected by anti-fibrinolytic agent, mortality rate is very high

- Dilutional coagulopathy and dilutional thrombocytopenia may develop after massive transfusion and massive fluid resuscitation

29

SUMMARY

- 3 most common causes of acquired coagulopathy

- 3 most common predisposing conditions of DIC

- Risk factors for Vit K deficiency

3 most common causes of acquired coagulopathy:

- DIC

- Liver disease

- Vitamin K deficiency

3 most common predisposing conditions of DIC

- Infection

- Malignancy

- Obstetric complications

Risk factors for Vit K deficiency

- Prolonged antibiotic therapy

- Malnutrition

30

T/F: Factors II, V, IX, and X are vitamin K dependent?

False; II, VII, IX, and X

31

T/F: In the setting of liver failure, factor VIII level is markedly decreased?

False

32

T/F: If fibrinogen is normal, DIC is ruled out?

False

33

T/F: If a pt has DIC, there is always a predisposing (or underlying) condition?

True

- DIC is always a secondary disease