Term
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Definition
Congenital deficiency of fibrinogen
OR acquired after hemodilution, blood loss and/or consumption, during DIC, or in sepsis.
Rx: infuse with FFP, cryoprecipitate, or fibrinogen concentrates
Normal: 1.5-3g/L |
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Term
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Definition
Deficiency of Factor V
1:1million
Auto recessive |
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Term
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Definition
Tendency to form clots
-pathologic thrombosis is primary cause of mortality in the US-
DVT, Pulm embolism, MI, stroke
Mutations in Factor V are most common hereditary cause
e.g. factor V leiden (R506Q), etc
Mutation makes it resistant to cleavage by activated protein C (APC resistance) --> remains active, increases rate of thrombin generation |
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Term
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Definition
deficiency of vWf (and Factor VIII)
-platelets can't adhere to endothelium
*Most common coagulation disorder*
-results in bleeding tendency of mucous membranes, most apparent in tissues having high blood flow shear in narrow vessels (nosebleeds, GI bleeding, menorrhagia)
-Most are hereditary
-Acquired: aortic valve stenosis, type IIA (Heyde's syndrome)
-Also leads to factor VIII deficiency |
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Term
| thrombotic thrombocytopenic purpura |
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Definition
TTP
Acquired (Ab-induced ADAMTS13-deficiency)
Congenital (absence of ADAMTS13)
-breakdown of vWf multimers + microangiopathic hemolytic anemia with fibrin deposition, platelet deposition, in small vessels, capillary necrosis
-brain most affected (TTP bites brain, nips, kidney)
Clinically: 30-50y/o, F>M, abrupt onset, 15% assoc with other dz
fever, pallor/anemia, hemorrhage, neurologic/renal abnormalities
Dx pentad (40% pts)
- thrombocytopenia
- MAHA (microangiopathic hemolytic anemia) - schistocytes, anemia, reticulocytosis, high LDH
- neurologic sx
- fever
- renal impairment
Path: hyaline thrombi in terminal arterioles/capillaries (made of vWf and platelets). UL-vWf multimers b/c absent ADAMTS13
Labs: high LDH, low haptoglobin, (-)DAT, blood smear with schistocytes, microscopic proteinuria and hematuria
ADAMTS13 low, IgG anti-ADAMTS13, UL-vWf multimers
Rx: Plasmapheresis (plasma exchange) to replace ADAMTS13 and remove anti-ADAMTS13 Abs; rituximab, follow platelet ct, LDH, sx, recombinant ADAMTS13, Eculizumab (mAb to C5 complement) |
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Term
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Definition
Lack of alpha granules
-contain factors involved with coagulation, inflammation, wound repair
Ghost-like appearance
Autosomal inheritance
Clinically: prolonged bleeding time
Labs: platelet aggregation normal (esp with AA and ristocetin, but variable with epi, collagen, ADP, thrombin)
Primary and secondary waves both decreased.
Mild thrombocytopenia, mod enlarged platelets.
Rx: platelet txfusion |
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Term
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Definition
Lack of delta granules
Presents with albinism (oculocutaneous)
Auto recessive
Puerto Rico |
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Term
| Glanzmann's thrombasthenia |
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Definition
*Aggregation problem*
-Deficiency of GPIIb/IIIa
deficient in platelet aggregation, can't bind to fibrinogen
-auto recessive, very uncommon
-clinically:
easy/large bruising, epistaxis, gingival bleeding, menorrhagia, complications w/pregnancy, trauma, surgery
Lab findingS:
normal platelet count/morphology, PROLONGED bleeding time, ABNORMAL platelet aggregation ---- only normal aggregation with Ristocetin; all other aggregates require GPIIb/IIIa
Rx: platelet txfusions, hormone therapy for menorrhagia, iron replacement therapy |
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Term
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Definition
*Problem with adhesion*
Deficient in GPIb (the vWf receptor on platelets)
- difficulty adhering platelets
-very uncommon (auto recessive)
-mild thrombocytopenia
-GIANT PLATELETS on smear (big suckers)
-Ristocetin aggregation absent (needs GP1b and vWf for aggregation)
-Clinical sx:
Bruising, epistaxis (nosebleeds), gingival bleeding, menorrhagia, complications w/trauma and surgery
Rx: platelet txfusions, estrogen therapy for menorrhagia |
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Term
| Deficiency of factor II (thrombin), V, VII, or X |
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Definition
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Term
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Definition
| Deficiency of Factor VIII |
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Term
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Definition
Deficiency of Factor IX (christmas factor)
AKA "Christmas DZ" |
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Term
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Definition
Platelets <20,000
Spontaneous hemorrhage
Petechiae, ecchymoses |
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Term
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Definition
Inability to turn off clotting
e.g. - Deficiency of ptns C and S
Exogenous clotting in microvasculature
-Warfarin skin necrosis (vit K antagonist, drops anti-coagulants II, VII, IX, X, ptns C and S)
-seen in neonates with ptn C and S deficiencies |
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Term
| Deficiencies of extrinsic factors (TF or VII) |
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Definition
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Term
| Deficiencies of intrinsic factors (VIII, IX, XI, XII) |
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Definition
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Term
| Deficiency of common pathway factors (X, V, prothrombin (II) |
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Definition
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Term
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Definition
Severe bleeding
-activated by thrombin and cross links fibrin monomers, α-2 antiplasmin into fibrin clots |
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Term
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Definition
Produce mutated Factor V (cofactor for Xa's activation of prothrombin, activated by thrombin, controlled protein C)
**Most common cause of inherited hypercoagulability**
-Mutated form can't be degraded by PtnC |
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Term
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Definition
These pts never bleed
-can't activate intrinsic pathway
-IX-->IXa by TF/VIIa from extrinsic pathway, to there's no functional deficit |
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Term
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Definition
Delta granule abnormality
Auto dominant
mild to moderate bleeding
ADP and serotonin can't be stored
Labs: normal platelet count/morphology, prolonged bleeding time, normal aggregation with ristoceetin and AA, abnormal with ADP, collagen, Epi, and thrombin
Rx: DDAVP (promotes release of vWf and factor VIII); platelet txfusions |
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Term
| Acquired platelet fxn disorder - ASA, NSAIDs |
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Definition
COX inhib impair crating TxA2
Alcohol prolongs bleeding time even more |
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Term
| Acquired platelet fxn disorder - Abx |
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Definition
| PCN, beta lactams (ticiarcillin, piperacillin) |
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Term
| Acquired platelet fxn disorder - cardiovascular drugs |
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Definition
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Term
| Acquired platelet fxn disorder - Uremia (renal insuff) |
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Definition
Platelets normal
Prolonged bleeding time
Increased guanidinosuccinic acid, phenols, NO (disrupt adhesion and aggregation)
Clinically: ecchymoses, GI bleeds, surgical bleeding
Rx: Dialysis (remove increased toxins), Cryoprecipitate (esp vWf:VIII), DDAVP, Estrogens |
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Term
| Sequestration of platlets |
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Definition
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Term
| Decreased production of platelets results from: |
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Definition
Drugs (myelosuppressive)
Alcohol - suppresses platelet prod at BM level
Deficiency of B12 or folate
Radiation
Aplastic anemia |
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Term
| Accelerated destruction of platelets results from: |
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Definition
Infection
DIC
Massive txfusion (dilution)
TTP (thrombotic thrombocytopenic purpura)
HUS (hemolytic uremic syndrome)
ITP (idiopathic thrombocytopenic purpura)
May Hegglin anomaly
Wiskott-Aldrich syndrome
HIT (heparin induced thrombocytopenia) |
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Term
| ITP (idiopathic thrombocytopenic purpura) |
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Definition
Immune-mediated (anti-platelet Abs)
-coated platelets destroyed in reticuloendothel system (spleen, liver, BM)
-platelet life is hours to days
Subtypes:
Acute-kids 2-3y/o, <6mos thrombocytopenia, often resolves itself, prodromal viral infection
Chronic: Adults, esp females, >6mos thrombocytopenia, requires Rx
Clinically: petechiae, ecchymoses, mucous membranes, menorrhagia, hematuria, melena (blood in stool), dental, surgical procedures
Evans syndrome - ITP w/Coombs+ autoimmune hemolytic anemia
Rx: Steroids (slow thinning of endothel cells, decreases size of fenestrations, blocks reticuloendothel cell consumption of sensitized platelets, reduces Ab production); splenectomy, IVIg (blocks reticuloendothelial system), Danazol, Rituximab, Cyclosporine A, Vincristine, Thrombopoeitin (Nplate, Pomacta) |
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Term
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Definition
Auto recessive
Mut in MYH-9
MACROthrombocytopenia
DOHLE bodies in neuts (blue discoloration) |
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Term
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Definition
XLR inheritance
MICROthrombocytopenia
eczema
Immunodeficiency
Rx: irradiated platelet txfusion
BMT |
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Term
| HIT (heparin-induced thrombocytopenia) |
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Definition
Abs to heparin-PF4 complex
-complex binds to Fc receptors --> intense platelet activation w/thrombocytopenia and hypercoagulable state
3-5% of pts exposed to standard porcine heparin
Occurs 5-14 days after exposure to heparin (first time) or within a few days (second time)
Complications:
Thrombosis (rarely, arterial thrombosis --> gangrene and amputatioin) (more common, venous thrombosis - DVT, PE, cerebral)
Labs: thrombocytopenia (<150,000) or decrease of 50% from baseline. ELISA is sensitive, not specific. GOLD STANDARD: SRA (serotonin release assay) - contained in delta granules, marker of platelet activation
Rx: stop heparin, give thrombin inhibitors (refludin, argatroban).
Hypercoagulable state can persist for 3 weeks, platelet count recovers in 3-5 days |
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Term
| Thrombotic Microangiopathy (TMA) |
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Definition
Causes: infection, stem cell txplant, HELLP syndrome, antiphospholipid Ab syndrome, vasculitis, txplant Rx, DIC, TTP (acquired/congenital), HUS (shiga-toxin induced and atypical)
Char by:
MAHA (microangiopathic hemolytic anemia)
thrombocytopenia (platelets consumed as they form small clots in vessels)
microvasc thrombosis w/platelets/fibrin
organ dysfxn |
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Term
| Familial TTP - Upshaw Schulman syndrome |
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Definition
See TTP
Congenital ADAMTS13 deficiency
Rx: prophylactic FFP infusions to restore ADAMTS13 |
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Term
| HUS (hemolytic uremic syndrome) |
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Definition
subtypes: shiga-toxin assoc, atypical HUS (genetic), secondary HUS
Triad: MAHA (microangiopathic hemolytic anemia), thrombocytopenia (mild), acute renal injury |
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Term
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Definition
E-coli O157:H7
Peak incidence in very young and very old
Course: acute onset diarrhea, hemorrhagic colitis, pallor, abd pain, vom, dark red/black urine
Pathogenesis: induced apoptosis in glomerular endothel cells --> chemokine/cytokine expression --> WBC inflammation --> endothel damage, microvasc thrombosis (from platelet and fibrin deposition); may bind complement inhib --> MAC activation
Organ damage results from decreased perfusion through glomerular endothel (from damage from fibrin deposits)
Labs: MAHA (DAT(-), hemolysis (high bilirubin, LDH, low haptoglobin), schistocytes); thrombocytopenia; renal failure (high BUN, creatine); stool culture - Stx gene detected by PCR
Rx: supportive, RBC txfusions for anemia, NO platelet txfusions, dialysis, eculizumab
Prognosis: 25% have neurologic involvement (stroke, seizure, coma), high mortality in older pts, decreased GFR, ESRD, HTN |
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Term
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Definition
identical sx to shiga-toxin assoc HUS
Affects children and adults, 25-37% familial
Triad: MAHA, thrombocytopenia, acute renal injury
Clinically: sudden onset, low HgB, low platelets, renal insufficiency, uncontrolled activation of alternative complement pathway)
Dx: rule out shiga-toxin assoc HUS
Rule out TTP (ADAMTS13 deficiency
Rx: plasma therapoy, eculizumab |
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Term
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Definition
| causes: infections, cancer, chemo, pregnancy, systemic dz |
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Term
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Definition
Acquired disorder of hemostasis
Vit K absorbed in ileum, requires bile salts
Causes
Sources 1/3 from Diet = (green leafy veggies - darker is better; chewing tobacco) 2/3 from intestinal flora
Fxn: co-factor in gamma carboxylation of Glu residues in Factors II, VII, IX, and X; Ca2+ bridges these factors with PLs to work.
Also activates Ptn C and S |
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