bleeding disorders Flashcards
some initial diagnostic testing that should be included for bleeding disorders
- CBC
- gives plt count
- Hgb - peripheral blood smear
- coagulation panel
- INR/PT/aPTT - CMP
coagulation panel includes:
PT
PTT
INR
(involves drawing blood, no fasting needed, no special instructions)
what is added to react with XIIa to start clotting through intrinsic/common pathway to evaluate PTT/aPTT
contact activator/phospholipid and Ca+
PTT/aPTT is very sensitive to ___
thrombin inhibition
(perfect for heparin (unfractionated))
- A one-stage clotting test, screens for coagulation disorders
- Standard part of a coagulation panel
partial thromboplastin time (PTT, aPTT)
PTT detects deficiencies of the ____ and may reveal defects in the ____
intrinsic, extrinsic
What is added to react with VIIa to initiate clotting through extrinsic/common pathway (for PT)?
thromboplastin (TF)
which factor has the shortest half-life
factor VII
what does prothrombin depend on?
vitamin K
what anticoagulant do you monitor with PT/intrinsic pathway
warfarin
if a pt has a high INR, what are they in a risk of? low INR?
bleeding
clotting
Disorders of primary hemostasis present with:
- mucous membrane bleeding
- epistaxis
- petechiae
disorders of primary hemostasis affect:
- bleeding time
- platelet count
Disorders of secondary hemostasis present with:
- hemarthrosis
- intracerebral hemorrhage
- deep tissue hematomas
disorders of secondary hemostasis affect:
- PT
- PTT
Mixed bleeding disorders can affect:
- bleeding time and platelet count
- PT and PTT
how can specific factor deficiency be determined?
Assessing the PT or aPTT in mixes of test plasma with commercially available plasmas deficient in known factors
which hemophilia is a congenital deficiency of coagulation factor VIII
hemophilia A
which hemophilia is a congenital deficiency of coagulation factor IX
hemophilia B
signs of hemophilia
recurrent hemarthroses and easy bruising/bleeding
(knees MC)
which hemophilia is MC X-linked genetic disease
hemophilia A
which hemophilia is X-linked recessive, leading to affected males and carrier females
hemophilia B
female carriers of hemophilia are usually
asx
Severe hemophilia usually presents in who? with ____ (s/s)
- infant males or in early childhood
- spontaneous bleeding into joints, soft tissues
mild hemophilia typically present with _______ than usually after a significant hemostatic challenge (surgery, trauma)
more bleeding
(spontaneous bleeding is rare)
what is the “double whammy”
Patients with hemophilia with deficiency in a clotting factor PLUS later develop inhibitors to those factors
the “double whammy” is more common in which hemophilia
A
how is the “double whammy” characterized?
- bleeding episodes that are resistant to treatment with clotting factor VIII or IX concentrate
- new or atypical bleeding
what are the labs for hemophilia?
- low factor VIII or factor IX activity level
- aPTT prolonged
- PT/INR normal
- CBC normal
normal hemostasis requires at least ___ (%) of factor VIII activity
25%
mild = 5<x<40%
moderate = 1-5%
severe =<1%
tx of minor bleeding of mild hemophilia A
DDAVP
(also for major + factor VIII)
tx of minor/major bleeding of moderate/severe hemophilia A
factor VIII
tx of minor/major bleeding of mild-severe hemophilia B
factor IX
mainstay tx for hemophilia?
- Plasma-derived or recombinant factor concentrates (mainstay)
- Celecoxib - arthritis symptoms
- opioid analgesics - pain control
severe hemophilia require what tx?
infusions of factor concentrate up to 3 times a week to prevent recurrent joint bleeding
what should be avoided when taking celecoxib?
other NSAIDs and aspirin
- increases risk of bleeding from inhibition of platelet function
what is the most common cause of death of hemophilia pts
- transfusion-obtained HIV/AIDS
- hepatitis/cirrhosis
MC life-threatening complications of hemophilia
intracranial hemorrhage and hemorrhages
what is the SECOND MCC of death in hemophilia pt
intracranial hemorrhage
what pt education must you give for hemophilia pts
- avoid contact sports
- monitor for s/s of bleeding
- home infusion technique
- prophylactic factor transfusions
- early tx of any bleeding
what is the most common inherited bleeding disorder
Von Willebrand Disease
a large multimeric glycoprotein that binds to its receptor, platelet glycoprotein Ib, bridging platelets together and tethering them to the site of vascular injury.
vWF
what is the most common type of vWD
type 1
which vWD type is a quantitative defect, with not enough vWF
type 1
which vWD is only autosomal recessive with a total or near total absence of vWF
type 3
most severe
which vWD is qualitative defect, with dysfunctional vWF
type 2
most common signs of vWD
nosebleeds
hematomas
prolonged bleeding from trivial wounds
women with vWD are 5x more likely to have ?
menorrhagia
lab findings of vWD
- “prolonged bleeding time”
- usually normal in vWD type I
- may be present but is not specific for vWD!! - slightly prolonged aPTT in half of pts bc of low levels of FVIII
- may be prolonged with severe form of vWD - Normal PT
(labs should be repeated to confirm abnormal results)
3 tx for vWD
- DDAVP
- rVWF
- vWF/FVIII
what are the congenital coagulation disorders (coagulopathies) (3)
- hemophilia
- vWD
- FXI deficiency
autosomal recessive
Jewish descent
mild bleeding
FXI def
tx for FXI def.
- FXI concentrate (if available)
- FFP (if no FXI concentrate)
when you make too few PLTs = inability to make a primary plug or secondary clot
thrombocytopenia
causes of thrombocytopenia
- increased destruction
- decreased production
- bone marrow failure
- chemo
- nutrition
common signs of thrombocytopenia
MALT bleeding
epistaxis, gum bleeding, GI bleeds (rare)
cerebral hemorrhage
petechial rash (non-blanchable)
cirrhosis can commonly cause?
hypersplenism = increased destruction of PLTs = thrombocytopenia
type of thrombocytopenia where PLT are being consumed by a patient (not a lack of production)
destructive or consumption
5 CC of destructive/consumption thrombocytopenia
- splenomegaly/hypersplenism - liver disease, lymphomas
- antibody-mediated destruction (ITP)
- drug-related (HIT)
- massive bleeding associated with consumption
- diffuse thrombus formation
patients form auto-antibodies against antigens on PLT surface
immune thrombocytopenic purpura (ITP)
ITP is usually seen in ?
children
if a healthy child presents with a sudden petechial rash, with bruising/bleeding, revealing signs of cutaneous bleeding, what are you suspicious of?
ITP
cutaneous bleeding = petechiae, purpura, ecchymoses
what is the diagonsis of ITP
- isolated thrombocytopenia (<100k)
AND - no clinical apparent associated conditions that may cause thrombocytopenia
MC management for ITP
watchful waiting - most children require no specific tx
some require pharmacologic intervention (rare)
avoid antiplatelet and anticoagulants until thrombocytopenia is resolved
when would someone need pharmacological intervention for ITP (3)
- severe thrombocytopenia (<10k), with signs of substantial cutaneous bleeding
- moderate thrombocytopenia (<20k), with mucosal bleeding
- past or anticipated factors that increase bleeding risk (recent head trauma)
if tx is necessary for ITP, what do you give?
- corticosteroids (FIRST LINE)
- oral prednisone, IV methylprednisolone, IV/oral dexamethasone
- (IVIG can be started first) - PLT transfusion for serious bleeding
- splenectomy sometimes
mechanism of drug-related PLT destruction is ?
immune-mediated mostly
typical presentation of drug-related destruction
thrombocytopenia
mucocutaneous bleeding 7-14d after exposure to a new drug
what kind of medication is well-known to cause drug-related destruction
ABX
tx for drug-related destruction
stop the drug
rare - immunosuppression (corticosteroids)
name of massive bleeding that can consume PLTs at rates beyond which they can be produced by bone marrow
can lead to DIC-like states
bleeding-associated consumption
tx for bleeding-associated consumption
blood product infusion
interventions to surgically stop bleeds
hypoproliferative thrombocytopenia MC arises from ?
bone marrow failure
4 hypoproliferative disorders
- leukemia/lymphoma/myelodysplasia/aplasia
- cancers metastatic to bone marrow
- severe viral infection
- radiation or chemo
tx for hypoproliferative thrombocytopenia
- episodic - resolves once over (viral)
- treat underlying cancer
- stem cell transplant (esp aplasia)
- bone marrow loses regenerative capacity
which class of PLT disorder has normal PLT count, but dysfunctional PLT
iatrogenic or acquired is common
qualitative
manifestations of qualitative PLT disorders
MALT bleeding
tx for most qualitative PLT disorders
transfusion of normal donor platelets
what drugs are the MCC of acquired PLT dysfunction
- aspirin
- clopidogrel
- NSAIDs
___ and ___ are irreversible inhibitors of PLT function, ___ induce reversible PLT dysfunction
Aspirin, clopidogrel - PLT have no function until CL (5-7d)
NSAIDs - PLT function returns 12-24h
2 thrombotic microangiopathies (TMAs)
thrombotic thrombocytopenic purpura (TTP)
hemolytic-uremic syndrome (HUS)
Pts with larger multimers of vWF, lack plasma protease in their plasma, and has antibodies against ADAMTS13 most likely have ?
thrombotic thrombocytopenic purpura (TTP)
common in adults
clinical presentations of TTP (3)
- neurologic dysfunction
- petechiae
- dark urine
TTP diagnostic lab evaluation
- WBC count - normal or higher
- 8-9 g/dL Hgb (decreased)
- schistocytosis
- PT and aPTT - normal
- D-dimer - normal or elevated
- fibrinogen - high
- direct coombs test - negative
tx for TTP
- FFP
- rituximab, corticosteroids, IVIG, vincristine, cyclophosphamide, and splenectomy
NO PLTS
MCC of acute renal failure in children
hemolytic uremic syndrome (HUS)
clinical syndrome characterized by progressive renal failure associated with microangiopathic hemolytic anemia and thrombocytopenia
hemolytic uremic syndrome (HUS)
MC clinical feature of hemolytic uremic syndrome
prodromal gastroenteritis - prodrome of fever, bloody diarrhea (2-7d) before onset of renal failure
MC of typical HUS? second?
E. coli serotype
shiga-like toxin [Stx-HUS]
Atypical HUS can be ___
sporadic or familial
lab findings of HUS
- BMP - elevated BUN/CR
- CBC - severe anemia
- schistocytes
- Bilirubin and LDH - elevated
obtain stool sample for E. coli and shigella
tx for HUS
typical - supportive
atypical - plasma exchange
essentials of DIC diagnosis
- frequent cause of thrombocytopenia in hospitalized patients
- prolonged aPTT and PT
- Thrombocytopenia and decreased fibrinogen levels
An uncontrolled local or systemic activation of coagulation, which leads to thrombocytopenia and depletion of coagulation factors and fibrinogen
disseminated intravascular coagulopathy (DIC)
etiology/causes of DIC
S = Sepsis
T = Trauma
O = Obstetric complications (ex: Preeclampsia)
P = Pancreatitis (Acute)
M = Malignancy (esp. Blood and brain cancers)
N = Nephrotic syndrome
T = Transfusion (hemolytic rxn)
clinical features of DIC
- Bleeding at multiple sites - intravenous catheters or incisions (purpura fulminans)
- purpura and petechiae
lab findings of DIC
- Prolongation aPTT and PT
- Low levels of fibrinogen
- D-dimer levels as well as other FDPs are elevated
- bc of activation of coagulation and diffuse cross-linking of fibrin. - Schistocytes
If persistent bleeding of DIC, consider use of ___; do not administer bolus.
heparin
If persistent bleeding of DIC, consider use of ___; do not administer bolus.
heparin
