Lecture 7: Bleeding Disorders Flashcards
What two things in the history help determine bleeding disorder etiology?
Bleeding site
Underlying bleeding tendency presence
What does a mucocutaneous bleed suggest?
Qualitative/quantitative platelet disorder
What does a joint or soft tissue bleed suggest?
Coag factor disorder
What should an initial panel of lab tests include to help determine bleeding disorder etiology?
CBC
Peripheral blood smear
Coag panel (INR/PTT/PT)
CMP
Additional:
Bleeding time
PFA-100
What is a PFA for?
Whole blood through a capillary with platelet agonists is measured.
More sensitive and reproducible than bleeding time.
What AC is measured with aPTT? Why?
UFH, because aPTT measures intrinsic pathway, which has thrombin.
What AC is measured with PT? Why?
Warfarin, because PT measures extrinsic pathway, which is more Vit-K dependent.
What other disease can PT monitor?
Liver, bc Vit K
What is INR?
International normalized ratio.
It is the ratio of PT to a standard sample.
What does high INR indicate?
Higher risk of bleeding.
What is the mnemonic for PTT and PT?
PTT = play table tennis (inside)
PT = play tennis (outside)
How are coag factors measured?
PT and aPTT can be compared in a sample plasma to a commercial plasma deficient in certain factors.
When do I use aPTT and PT tests together?
To monitor the transition between heparin and warfarin
What does a primary hemostasis disorder affect?
Mucous membrane bleeding, epistaxis, and petechiae.
Affects bleeding time and platelet counts.
What does a secondary hemostasis disorder affect?
Hemarthrosis, intracerebral hemorrhage, and deep tissue hematomas.
Affects PT and PTT.
What is hemophilia A?
Congenital deficiency of Factor 8. (vWF related)
What is hemophilia B?
Congenital deficiency of Factor 9
What kind of inheritance is hemophilia A?
X-linked recessive
1 in 5000 male live births
What kind of inheritance is hemophilia B?
X-linked recessive
1 in 25000 male live births
How do female carriers of hemophilia present?
Asymptomatic.
How does severe hemophilia present commonly?
Early childhood spontaneous bleeds into joints or soft tissues.
How does mild hemophilia present commonly?
Excess bleeding post hemostatic challenge like surgery.
What is the secondary concern in patients with hemophilia?
They can develop inhibitors to the factors they are deficient in.
30% in A
5% in B
How does factor inhibition present in hemophiliacs?
Bleeding episodes resistant to factor 8 or 9 concentrate.
How do we diagnose hemophilia?
Low factor 8 or 9 ACTIVITY.
Prolonged aPTT
Note:
NORMAL PT/INR
NORMAL CBC
How much activity of the factors does hemostasis normally require?
At least 25%
What is considered mild factor 8 activity?
5-40%
How do I treat a bleed in a mild hemophilia A?
DDAVP
How do I treat bleeds in a moderate-severe hemophilia A?
Factor 8 concentrate
How do I treat bleeds in hemophilia B?
Factor 9 concentrate
DDAVP DOES NOT WORK.
What is a common NSAID used to treat hemophilia?
Celebrex only. COX-2 inhibitor
How often do hemophilia patients require factor concentrate infusions?
up to 3x a week
What other med is common for a hemophiliac to take besides celebrex?
Opioid analgesics
What is the leading cause of death in hemophiliacs?
Transfusion-obtained HIV/AIDS
Hepatitis/Cirrhosis
What is the second leading cause of death in hemophiliacs?
ICH
It is also the most common cause of death dt hemorrhage.
What is the prognosis for a mild hemophiliac?
Normal life if they are treated prophylactically.
What are counseling tips for hemophiliacs?
AVOID CONTACT SPORTS
Monitor body for bruising/etc
Home infusion technique
Have a hematologist and hemophilia center you attend regularly.
What is the most common inherited bleeding disorder?
vW disease
What are the types of vWD?
Type 1 = Quantitative defect
Type 2 = Qualitative defect
Type 3 = Profound quantitative defect.
How is vWD inherited?
1 is autosomal dominant
2 is autosomal dominant primarily, recessive sometimes.
3 is autosomal recessive.
What is the most common type of vWD?
Type 1 (75% of cases)
What vWD type presents similarly to hemophilia A?
Type 3
What are the most common signs of vWD?
Nosebleeds and hematomas
What is a concern in women with vWD?
Menorrhagia is 5x more likely.
How does bleeding time present in vWD?
Can be normal in type 1.
Non-specific.
How does aPTT present in vWD?
Mildly prolonged in only half of pts.
How does PT present in vWD?
Normal.
What kind of blood type has the lowest levels of vWF?
Type O
):
What causes levels of vWF to vary from person to person?
Stress
ABO type
What is the treatment protocol for vWD?
DDAVP
rVWF
vWF/F8 concentrates
DDAVP is only for mild.
What is factor 11 deficiency sometimes known as?
Hemophilia C.
How is Factor 11 deficiency inherited?
Autosomal recessive.
Most prevalent among Ashkenazi jewish descent.
How does Factor 11 deficiency present?
Mild bleeding.
How is Factor 11 deficiency treated?
F11 concentrate.
FFP if no concentrate available.
What are the two primary causes of thrombocytopenia?
Increased platelet destruction
Decreased platelet production
What can cause increased sequestration of platelets?
Hypersplenism
What are common causes of a destructive or consumption thrombocytopenia?
Splenomegaly/hypersplenism
Antibody mediated destruction
Drug related destruction
Massive bleeding associated with consumption
Diffuse thrombus formation
What is ITP?
Immune thrombocytic purpura
Auto-antibodies against antigens on the PLT surface, causing destruction.
When is ITP commonly seen?
60% in children post URI
Rare in adults
Diagnosis of exclusion
How does ITP present?
Sudden appearance of petechial rash in an otherwise healthy child.
PE should reveal cutaneous bleeding (also mucosal bleeding common in 40%)
What is the most severe consequence of ITP?
ICH
How is ITP diagnosed?
Isolated thrombocytopenia with no other apparent causes.
ITP = ISOLATED
What are the initial labs for ITP?
CBC and peripheral blood smear
Findings INCONSISTENT with ITP
How do you manage ITP?
Watch it.
Intervene if any life-threatening stuff happens.
AVOID ACs and APs until thrombocytopenia is cleared.
Refer to heme :)
What is the treatment for ITP if needed?
Corticosteroids FIRST LINE
IVIG can be added.
Platelet transfusions can be given for serious bleeding.
Splenectomy may be necessary if >6mo duration.
What is the underlying mechanism in drug-related platelet destruction?
Immune-mediated.
How does drug-related platelet destruction present?
Severe thrombocytopenia & mucocutaneous bleeding 7-14 days post exposure to new drug.
What is the primary drug class to be wary of in drug-related platelet destruction?
Antibiotics
How is bleeding-associated consumption treated?
Blood product infusion and stoppage of bleeds.
What is the most common cause of hypoproliferative thrombocytopenia?
Bone Marrow Failure (AKA lack of PLT production)
What is the tx for hypoproliferative thrombocytopenia?
Infectious/viral should return to normal on its own.
Malignancies may require cancer tx.
Aplasia will require stem cell transplant.
What kind of platelet disorder is ITP, drug-induced thrombocytopenia and hypoproliferative thrombocytopenia?
Quantitative
What is the most common type/origin of qualitative PLT disorders?
Iatrogenic or Acquired.
Congenital is rare.
What is a lab test that helps determine qualititative PLT disorders well?
Peripheral blood smears.
How do qualitative plt disorders typically manifest initially?
Mucous membrane bleeding
How are most qualitative plt disorders treated?
Platelet infusion
What is the most common iatrogenic cause of qualitative plt disorders?
ASA
Plavix
NSAIDs
What drugs cause irreversible plt dysfunction?
ASA and Plavix.
Must wait for PLTs to be cleared.
What drugs cause reversible plt dysfunction?
NSAIDs.
Function returns in 12-24 hrs.
If we have an emergency and a patient was still on plavix prior to surgery with a qualitative plt defect, what should we do?
PLT infusion should be sufficient to overcome acquired defect.
What are the two types of Thrombotic microangiopathy?
TTP
HUS
What are the primary characteristics of thrombotic microangiopathy?
Incorporation of plts into the microvasculature.
Shearing of erythrocytes in microcirculation results in microangiopathic hemolytic anemia
What is the main cause of TTP?
Unknown.
HOWEVER…
Usually have large multimers of vWF and lack ADAMTS13, which is the protease to break it down.
Who is TTP more common in?
Adults
Who is ITP more common in?
Children post URI
How does TTP present?
Neurologic dysfunction (Stroke-like presentation)
Petechiae
Fever (50%)
Hemoglobinuria
What is uncommon in TTP presentation?
Severe bleeding.
How is TTP diagnosed?
CBC with minor leukocytosis, minor Hgb depression, and thrombocytopenia.
Peripheral smear should show mod-sev schistocytes
Normal PT/PTT
Normal - mild D-Dimer
High fibrinogen
LDH and bilirubin elevation to check hemolysis status.
NEGATIVE direct Coombs.
What is the treatment for TTP?
Plasma exchange via FFP.
If no exchange possible, FFP is sufficient until transferred.
What is the mortality of TTP without an FFP transfusion?
95%
What is in second-line treatment for TTP?
Rituximab, corticosteroids, IVIG, vincristine, cyclyphosphamide, and splenectomy
How is HUS characterized?
Progressive renal failure with associated hemolytic microangiopathy and thrombocytopenia.
What is HUS the most common cause of?
Acute renal failure in CHILDREN.
What is the primary pathophysiological event in HUS?
Endothelial cell damage
How does HUS commonly present?
Prodromal GE with fever and bloody diarrhea for 2-7 hrs prior to onset of renal failure.
How does typical HUS categorize as?
Shiga-like toxin (Stx) secondary to E Coli serotype 0157:H7
How is HUS diagnosed?
BMP w/ elevated BUN/CR
CBC with severe anemia and thrombocytopenia.
Peripheral smear with schistocytes.
Bilirubin/LDH elevation.
Stool sample for E.coli and shigella
How is HUS treated?
Typical HUS is supportive care only.
Atypical is Plasma exchange.
What are the key differences between HUS and TTP?
HUS usually has no fever post GE phase and present with antecedent GE.
What is DIC caused by?
Uncontrolled/systemic activation of coagulation, causing thrombocytopenia and depletion of coag factors and fibrinogen.
AKA you clot so much that you can’t clot anything after.
What is the mnemonic for DIC causes?
STOP Making New Thrombi
Sepsis
Trauma
Obstetric complications (pre-eclampsia)
Pancreatitis (acute)
Malignancy (blood/brain)
Nephrotic syndrome
Transfusion (Hemolytic reaction)
How does DIC present?
Bleeding at multiple sites.
Purpura fulminans
Petechiae
How is DIC diagnosed?
Elevated PT and PTT
Low levels of fibrinogen
D-dimer elevated and FDPs
Schistocytes in 10-20% of pts.
What are the main tx options for DIC?
Get plts above 20k or 50k if ICH
Cryoprecipitate
FFP
PRBCs
What is the secondary tx option for DIC?
Heparin in persistent bleeding, NO BOLUS
