8/20- Acquired Bleeding Disorders Flashcards
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
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
Local vs. systemic bleeding (what do they suggest?)
- Single area suggests a structural defect
- Multiple sites suggest a systemic defect
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
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
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
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)
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
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
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
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)
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
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
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.
What is shown here?
PBS with Schistocytes (fragmented RBCs)
What is included on the DIC panel?
- PT
- PTT
- Fibrinogen
- Thrombin time
- D-dimer
- Platelet count
(Positive) results of DIC panel?
- PT: elevated (consumption coagulopathy)
- PTT
- Fibrinogen
- Thrombin time
- D-dimer: elevated (hypercoagulable state)
- Platelet count
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
Treatment of DIC?
- Treat underlying cause
- Supportive care (maintain BP, etc.)
- Replacement therapy for bleeding (FFP, cryoprecipitate, and/or platelet transfusions)
- Heparin (only when thrombosis dominant picture)
- Antifibrinolytic agent (controversial)
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
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
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?)
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)
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)
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)
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
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
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
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
T/F: Factors II, V, IX, and X are vitamin K dependent?
False; II, VII, IX, and X
T/F: In the setting of liver failure, factor VIII level is markedly decreased?
False
T/F: If fibrinogen is normal, DIC is ruled out?
False
T/F: If a pt has DIC, there is always a predisposing (or underlying) condition?
True
- DIC is always a secondary disease
