1/6 Platelet and Bleeding Disorders - Carr Flashcards
quantitative vs qualitative platelet disorders
quantitative: low platelet count
qualitative: right number of platelets but incorrect fx
thrombocytopenia
low platelet count
- decreased production (marrow issue)
- congenital (rare)
- acquired (infection, meds, alcohol, marrow failure, bone marrow infiltration)
- increased destruction (decr half life)
- sequestration
neonatal immune thrombocytopenias
- neonatal autoimmune thrombocytopenia
- maternal SLE or ITP
- passive transfer of maternal IgG
- tx: IVIG
- neonatal isoimmune (NATP)
- incopatibility of fetal and maternal platelet antigens
- most commonly P1A1
- high risk of recurrence with future pregnancy
- tx: maternal platelets, IVIG
nonimmune platelet destruction
mechanical platelet destruction
- microangiopathic hemolytic anemia
- disseminated intravascular coag
- TTP: thrombotic thrombocytopenia purpura
- congenital absene or antibody to VWF protease ADAMTS13
- HUS: hemolytic uremic syndrome
- E. Coli 0157:H7
DIC
disseminated intravascular coagulation
“consumptive coagulopathy”
- pathological activation of coag
- initated by formation of small clots inside blood vessels throughout the body
- clots consume available coag proteins, anticoags, and platelets
- resulting acquired deficiency in clotting proteins and platelets → abnormal bleeding
causes
- conditions that introduce TF in circulation (trauma, cancer, obstetrical complications)
- endothelial damage
- stagnant blood flow
- infection
lab (Pathoma)
tx
- treat underlying disease
- replete consumed factors
- heparin (in acute promyelocytic leukemia, thrombosis)
- ATIII concentrates
TTP
cause
pentad
thrombotic thrombocytopenia purpura
cause: ADAMTS13 deficiency/absence
- normally ADAMTS13 cleaves vWF into smaller monomers for degradation
- uncleaved multimers (in TTP) → abnormal platelet adhesion
- can be genetic (rare, auto recessive deficiency) or acquired (antibody against protein, usually in adulthood)
pentad of TTP
- thrombocytopenia
- microangiopathic hemolytic anemia
- CNS disturvance
- renal failure
- fever
see…
- thrombocytopenia
- schistocytes
- elevated LDH
80% of patients die if not treated
- replace ADAMTS13
- remove circulating andibody
HUS
hemoytic uremic syndrome
E. Coli 0157:H7 (fecal contamination of food)
looks v similar to TTP
- no neuro features
- bloody diarrhea
- renal failure dominates
ddx: TTP vs DIC
3 tests and diff outcomes
coagulation screens
- TTP: normal
- DIC: abnormal
fibrinogen level
- TTP: normal
- DIC: low
fibrin split (degradation) products
- TTP: minimal/no elevation
- DIC: elevated
sequestration as a cause of thrombocytopenia
key sign
key: enlarged spleen w low platelet count
qualitative defects
disorders of adhesion
primary defect in platelet-vesselwall interaction
- Bernard Soulier syndrome: GP1b deficiency (platelet receptor for vWF)
- von Willebrand disease
vWF
types of von Willebrand disease
von Willebrand factor
- binds platelet GP1b
- binds collagen
- binds and stabilizes factor VIII
types of disease
- deficiency of vWF (types 1, 3)
- partial deficiency (Type 1), 70-80% of all cases
- severe/complete def (Type 3)
- dysfx protein (type 2)
- improper assembly of protein (2A)
- change of binding to platelet Gp1b (2B, 2M)
- decr factor VIII binding (2N)
enhanced binding of vWF by platelet
2A, 2B, 2N are key
disorders of aggregation
primary defects in platelet-platelet interaction
- congenital afribrinogenemia: absence of plasma fibrinogen
- Glanzmann thrombasthenia: deficiency/defect in GPIIb/IIIa
disorders of storage granules
- disorders of alpha-granules
- gray platelet syndrome: absence of alpha granules
- Paris-Trousseau (Jacobsen syndrome): giant alpha granules
- arthrogryposis-renal dysfx-cholestasis: deficiency in alpha granules
- deficiencies of dense granules
- Hermansky Pudlak syndrome: absence of dense bodies, mutations of HPS gene
- common in Puerto Rico
- oculocutaneous albinism, variable bleeding, ceroid accumulation (intestines, lungs, kidneys)
idiopathic dense granule disorder
“storage pool disease”
- attributed to defect in dense granules on basis of platelet aggregation and release studies
- prob most common platelet defect
- possibly defect of intracellular signaling
coagulation disorders
hemophilia
1. hemophilia A: factor VIII deficiency
2. hemophilia B: factor IX deficiency (aka Christmas disease)
X linked
- hallmark: bleeding into muscles and joints (ankles, knees; starts after crawling/walking age)
- can present in infancy
tx: recombinant or endogenous factor replacement
* issue: INHIBITORS: neutralizing antibodies against infused factor product
factor XI deficiency
“hemophilia C”
autosomal recessive
common in Ashkenazi Jewish pops
mucocutaneous bleeding (not muscle or joint)
factor XIII deficiency
extremely rare
lack of fibrin cross-linking leads to reduced clot stability and strength
classic presentation in infancy (bleeding from umbilical stump, intracranial hemm)
clinical test: urea clot lysis time
PT and PTT are normal!
two acquired factor deficiencies
- vitamin K deficiency
- affects II, VII, IX, X
- causes: antibiotics, malabsorption, hemmorhagic disase of infancy
- DRUGS: warfarin, coumadin, rat poison
- liver disease
- affects: II, VII, IX, X
- factors V, fibrinogen
- factor VIII preserved
coagulopathy of liver disease
- decreased clotting factor levels
- decreased platelets (enlarged spleen/sequestration)
- decreased natural anticoag
- abnormal blood vessels: esoph and rectal varices
- decreased clearance of activated clotting factors
- decreased clearance of clot breakdown pdts
- production of abnormal fibrinogen
mixing studies
help differentiate whether prolonged PTT is due to deficiency or inhibitory antibody
look at slides 117-120
TFPI
tissue factor pathway inhibitor
controls extrinsic pathway
antiphospholipid antibodies
phsopholipid is added to tube as part of PTT assay
ab which cross reacts with phospholipid in PTT will cause prolongation → mixing study will stay prolonged
deficiencies of controlling proteins increase the risk of thrombosis
4 ex
antithrombin deficiency
protein C deficiency
protein S deficiency
TFPI deficiency
purpura fulminans
severe protein C deficiency
- presents within hours of birth: unmeasurable PC
- rapid progression to DIC
- purpuric lesions at pressure points → palpable black eschars
- often blind infants from vitreal vein clot
- prenatal arterial ischemic stroke
inherited predisposition to thrombosis
Factor V Leiden : resistant to to inactivation by APC
prothrombin 20210A
