Disorders of Hemostasis Flashcards
Infusion of platelets
used to treat bleeding caused by thrombocytopenia or dysfunctional platelets
Fresh Frozen plasma
provides replacement coagulation factors & contains all coag factors
used for patients w/ multiple factor deficiencies
Cryoprecipitate
concentrate of fibrinogen, vWF, factor VIII, factor XIII
used for the replacement of fibrinogen & factor XIII
historically used as treatment of von willebrand disease & FVIII deficiency
* blood borne viruses cannot be inactivated
Factor concentrates
from either human plasma or genetically engineered cell line
individual concentrates are not availalbe for all factors
Prothrombin complex concentrates (PCC)
made from human plasma & includes factors: II, VII, IX, X (vit K def)
suitable for individual deficiencies of factor II, IX, X
Desmopressin (DDAVP)
synthetic hormone used to promote the release of vWF in patients w/ von willebrand disease, mild hemophilia A (FVIII) & thrombocytopenia
Petechiae
pinpoint bruising, small red to purple spots in the skin
Ecchymoses
bruises larger than 3 mm red to purple when first formed & become yellowish green as they heal
Hematoma
bruise that occurs when blood leaks from an opening in a vessel & collects beneath intact skin, blue or purple & slightly raised
Acquired Disorders of the Vascular System
purpura due to decreased connective tissue: scurvy, excess glucocorticoids
purpura due to vasculitis: drugs/infection
Quantitative platelet disorders
thrombocytopenia: primary & secondary
Functional Platelet disorders
- bernard-soulier disease
2. Glanzmann’s thrombasthenia
Thrombocytopenia: Decreased platelet production
bone marrow function is abnormal 3 causes: megakaryocyte hypoplasia (aquired) ineffective thromopoiesis (inherited) hereditary condition affects ability of bm to support megakaryocyte growth
May Hegglin anomaly
inherited cause of thrombocytopenia- lack of adequate bm megakaryocytes
large plts
dohle bodies present
Thrombocytopenia: accelerated or increased plt destruction
most common cause of thrombocytopenia
destruction can be immune (ITP, NAIT, HIT) mediated & nonimmune (TTP, DIC, HUS)
ITP (immune thrombocytopenic purpura)
common disorder causing severe thrombocytopenia
an autoimmune disorder in which autoreactive antibodies bind to platelets
Acute ITP
disease of children!
usually follows viral infection
spontaneous remission
lab <20x10^9/L
Chronic ITP
disease of young adults female > male plt count: 30-80x109/L mucosal bleeding duration of month or years
NAIT
immune plt destruction by alloantibodies that are stimulated by foreign antigen during pregnancy
similar to HDN except antibodies are directed towards plt antigens
Heparin Therapy thrombocytopenia
decrease in plt count is either:
- heparin associated thrombocytopenia (HAT)
- heparin induced thrombocytopenia (HIT)
Heparin associated thrombocytopenia (HAT)
non-immune, benign & limited thrombocytopenia
not associated w/ bleeding
Heparin-induced thrombocytopenia (HIT)
immune mediated adverse effect of heparin that increases risk of thrombosis
develop an IgG antibody to heparin-plt 4 complexes
associated w/ bleeding
Hemolytic-uremic syndrome (HUS)
more commonly found in young children
90% of cases caused by Shigella dysenteriae or E. coli
toxins from bacteria attach themselves to glomerulus cells, damages the cells, leads to formation of thrombi in renal vasculature
HUS lab results
hemolytic anemia!
schistocytes
renal failure
thrombocytopenia
Thrombotic thrombocytopenic purpura (TTP)
rare but often fatal; women > men; 30-40 yrs
50% have a history of a virus prior to onset
thrombotic lesions from arterioles & capillaries using up available plts
results in thrombus in organs (!)
TTP lab results
neurological manifestation
PT normal
APTT normal
fibrinogen, FDP, D-dimer normal
Disseminated intravascular coagulation (DIC)
body’s blood clotting mechanism are activated throughout the body
fibrin formation w/in the blood vessels leads to plt activation & consumption!
DIC lab results
Prolonged PT, APTT, TT
increased FDPs & D-dimer
decrease in fibrinogen
Primary thrombocytosisor Essential Thrombocytosis
neoplastic stem cell disorder causing dyregulated production of large #s of abnormal plts
Primary thrombocytosis or Essential Thrombocytosis lab values
increased plts
abnormal plt shapes
hemorrhages
Secondary thrombocytosis
caused by another disease or condition
normal plt morphology
elevated thrombocytosis
Bernard-Soulier Syndrome (BSS)
rare hereditary disorder of platelet adhesion
‘giant plt syndrome’
decrease in amount or abnormal function of the GPlb/IX complex
prevents adhesion!
Bernard-Soulier disease lab results
normal or decreased plt count
platelet aggregation test is abnormal with RISTOCETIN! (normal w/ others)
giant plts
Glanzmann’s thrombasthenia
rare hereditary disorder
aggregation does not occur!
def. of GPlb/IIIa complex - site of attachment of fibrinogen to plt surface
plt aggregation test is abnormal w/ ADP, collagen & epinephrine!!
Signs/symptoms of coag pathway factor deficiency
excessive bleeding following trauma, uncontrolled menstrual bleeding, vomiting blood, nosebleeds, unexplained hematomas
Clotting factor disorders grouped by (3)
autosomal recessive disorders
sex-linked disorders
autosomal dominant disorders
Autosomal Recessive disorders
Factor I (fibrinogen) deficiency Factor II (prothrombin) deficiency Factor V (proaccelerin) deficiency Factor VII (proconvertin) deficiency Factor X (Stuart) deficiency Factor XI (plasma thromboplastin antecedent) deficiency Factor XII (hageman) deficiency Factor XIII (fibrin stabilizing) deficiency Prekallikrein (fletcher) deficiency HMWK (Fitzgerald) deficiency
Factor I (fibrinogen) deficiency
autosomal recessive
2 forms: Afibrinogenemia & hypofibrinogenemia
Afibrinogenemia
no functionally detectable fibrinogen found
more severe @ birth & can lead to death (bleeding from umbilical cord etc)
increased PT, PTT, & TT
decreased fibrinogen
would be corrected w/ mixing study
Hypofibrinogenemia
few bleeding symptoms
normal PT, APTT
abnormal TT
normal fibrinogen
Factor II (prothrombin) deficiency
mild hemorrhaging rarest bleeding disorder increased PT, PTT normal TT, BT 2 types: congenital & acquired is more common
Factor V (proaccelerin) deficiency
mild to moderate bleeding w/ bruising
increased PT, PTT
normal TT
diagnosis made w/ factor V assay
Factor VII (proconvertin) deficiency
mild to moderate bleeding
increased PT * only coag factor deficieny in which PT alone is prolonged!***
diagnosis made w/ factor VII assay
Factor X (stuart) deficiency
mild to severe bleeding increased PT, PTT normal TT diagnosis made w/ factor X assay *** may want to exclude vit K deficiency before diagnosis
Factor XI (plasma thromboplastin antecedent) deficiency
Hemophilia C mild bleeding after trauma normal PT, TT increased PTT! diagnosis made w/ factor XI assay 2nd most common bleeding disorder affecting females!
Factor XII (Hageman) deficiency
asymptomatic NO BLEEDING
normal PT, TT
increased PTT
Factor XIII (Fibrin stabilizing) deficiency
umbilical cord bleeding & delayed healing
normal PT, PTT, TT
lab diagnosis relies on dissolution of the fibrin clot in 1% monochloroacetic acid or 5 M urea
Prekallikrein (fletcher) deficiency
asymptomatic!
normal PT, TT
increased PTT
HMWK (Fitzgerald) deficiency
asymptomatic!
normal PT, TT
Increased PTT
Sex-Linked Disorders
Factor VIII deficiency (hemophilia A)
Factor IX deficiency (hemophilia B)
Factor VIII deficiency
sex-linked hemophilia A effects males normal PT increased PTT musculoskeletal lesions, neurological deficiencies
Factor IX deficiency
sex linked hemophilia B
less common than hemophilia A but presents the same
Autosomal Dominant Disorders
von Willebrand Disease
Von Willebrand Disease
plts are intrinsically normal but exhibit abnormal adhesion bc of the absence or dysfunction of vWF & results in decreases in factor VIII & abnormal secondary hemostasis
very variable
3 types
Type 1 vWF disease
autsomal dominant
70% of all cases
quantitative decrease in vWF
mild bleedign
Type 2 vWF disease
variable inheritance
abnormality in structure of vWF
type 3 vWF disease
rare autosomal recessive absent levels of vWF
severe bleeding - similar to hemophilia A
vWF disease screening test
- bleeding time
- platelet function analyzer (replacing BT)
- APTT -typically increased
- plt count -normal
- PT- normal
vWF specific tests
- measurements of plasma vWF antigen
- factor VIII activity
- assays of vWF plasma activity
all are decreased!!
vWF disease treatment
cryoprecipitate or DDAVP
Acquired disorders of secondary hemostasis
DIC
acquired pathologic inhibitors
liver disease
vit K deficiency
If every test (primary & secondary hemostasis) are abnormal what should you suspect first?
DIC
Pathological inhibitors
single coagulation factor inhibitor lupus anticoagulant (LA)
Inhibitors of single factors
usually seen in patients w/ inherited factor deficiencies
neutralizing antibody directed against specific coag factors leading to a loss of activity
common inhibitors are VIII & IX
Diagnosis of inhibitors
APTT markedly prolonged
mixing study
assays for specific inhibitors
Lupus Anticoagulant
nonspecific, usually does not cause bleeding problems
associated w/ autoimmune diseases, neoplasms etc
react w/ phospholipid surfaces of test reagents used in the APTT - prolongs test results
