Disease & Def Patho/Mech Clinical S/S Dx/ Tests/Labs Tx Notes

Platelet or Petechiae For PLT fx: Other findings in

Vessel Mucosal bleeding NEVER order bleeding plt dysfx:
disorder: Bleeding from sf time test -Menorrhagia,
scratches 1. PFA (plt fx analysis) hematuria
Epistaxis (MC S/S) -Bleeding from
Easy bruising 2. Plt aggregation study tooth extraction
sites
-GI & intracranial
blding
Coagulation Inherited defect: Deep hematomas 1. aPTT: Factor inhibitors:
disorder: deficiency affecting Hemarthroses Intrinsic pthwy + common 1. Ab (esp w/
single clotting factor Delayed bleeding pthwy (XII, XI, IX, VIII) FVIII)
2. meds: heparin
Acquired defects: Coaguation defect: 2. PT: 3. non-specific
affect multiple a) Lrg post-traumatic Extrinsic pthwy Ab: lupus
coagulation factors; due ecchymoses or (VII)/common anticoagulant (not
to decreased synthesis hematomas - INR: standardized PT clinically
(ex-Vit K defic) b) Prolonged results significant)
or shortened half life (ex- bleeding after
DIC) laceration or any 3. Thrombin time:
(may see prolonged PT surgical prodceure - tests conversion of
& PTT) c) Bleeding into GI fibrinogen to fibrin
& urinary tracts - do w/ elevated PTT (rule
XLR: factors VIII & IX d) hemarthroses out dysfibrogenemia)
e) retroperitoneal &
all others: autosomal & deep muscle 4. Mixing studies:
recessive, except bleeding -do w/ nml PT, abn PTT
vWF = AD - distinguish betw factor
ex) pt who oozes deficiency & inhibitor
blood for days post -PTT resolves w/ add
dental procedure plasma = factor
deficiency; no change =
inhibitor

Activated abn fV w/ (m) that alters recurrent venous nml: PTT w/ APC --> Coumadin MCC of
Protein C specific cleavage site for thrombosis & PTT should increase; for hereditary
Resistance Protein C --> fV not thromboembolism In APCR: no increase in prevention thrombophilia
(Factor V inactivated PTT when APC added (5% of
Leiden) -DNA probe for Leiden Genetic caucaisans)
htz: 7x inc risk thrombus, variant of fV counseling
htz + OCP: 35x, hmo: 60% of hereditary
80x Compression TE:
stockings fV Leiden
Prothrombin
polymor.
(m) Protein C, S,
Antithrombin III
Disease & Def Patho/Mech Clinical S/S Dx/ Tests/Labs Tx Notes
Anti-ppl Ab auto IgG, IgM or IgA vs. usually asympto w/ PTT (artifact of lab Prevent PE: Anti-ppl Ab a/w
syndrome coag Ps that bind ppl anomalies in lab data testing) -LMWH 1st, SLE = Anti-
(APS) (beta2-GP1, -paradoxcial b/c would then shift to Cardiolipin Ab
prothrombin, apoH) recurrent venous & expect clotting deficiency Coumadin ("lupus
arterial TE @ young vs. tendency (INR ≥ 3) anticoagulant);
sometimes associated w/ age: fetal loss w/ causes false
SLE, AI dz (RA), or infarct placenta, PE, Anti-Cardiolipin Ab -no OCPs positive syphillis
meds MI, stroke, low plts levels test
(Pronestyl/procainamide) PC
Prothrombin G-->A (m) at 3'UTR of possibly: ANA, anti- 2nd MCC of
20210A prothrombin gene --> ssDNA, Coombs hereditary
transition elevated prothrombin thrombophilia (2-
levels, increase venous 3% of population)
thrombi
Methylene results in moderate PT: nml PTT: nml decrease
tetrahydrofolat increase in homocysteine homocystein
e reductase levels, a/w both arterial e w/
(m): & venous thrombus supplement
-homocysteine folate,
inactivates proteins C&S vitamins B12
Acute ITP: Plt AutoAb (IgG) vs. Abrupt onset 1-3 wks PC:  & B6
Self-limited;
Immune GpIIB-IIIa (TII HS rxn) after a viral BT:  usu resolves
Thrombo- -target for phago at infection. PT & PTT: nml spontaneousl
cytopenic spleen Present with y w/in 6 mos
Purpura epistaxis, easy Meas anti-platelet Abs
Most common cause bruising, petechiae Glucocorticoi
thrombocytopenia in (esp at lower body) no need for BM bx ds if severe
children 2-6 years of age (but would show
NO increased
lymphadenopathy or megakaryocytes)
splenomegaly
Chronic ITP IgG antibodies directed Insidious onset PC:  Complications:
against GpIIb-IIIa -Petechiae, esp at BT:  Splenectomy intracranial &
receptors at plts (type II dependent areas PT & PTT: nml (if severe; subarachnoid
HS) -may blend spleen = hemorrhages
->ecchymoses Plt Ab test: req 2-3 wks major site of
Most common cause of -Oft hx of easy for result phago
thrombocytopenia in bruising, nosebleeds, removal)
adults blding gums BM: nml/inc
megakaryocytes (response
Most common in women May present w/ to low plt count)
(3:1) 20-40 years of age melena, hematuria, -would NOT get BM bx
menorrhagia
PB: lrg platelets in PB =
NO splenomegaly or signs of inc plt destruction
l.node enlargement
Disease & Def Patho/Mech Clinical S/S Dx/ Tests/Labs Tx Notes
Heparin Type 1: (most)- due to Type 1: see Type II: Complications:
Induced direct plt aggregating thrombocytopenia Discontinue possible limb loss
Thrombo- effect of heparin immediately after therapy & due to clots at
cytopenia start tx; little clinical switch to large arteries; PE
(HIT) Type II: = AI consequence non-heparin from DVT
Ab vs. heparin-PF4 anticoagulant (serious!)
cmplx; binding activat Type II: see 5-14
platelets --> thrombosis, days after start tx;
even w/ low plts

HIV One of MC hematologic

Associated manifestations of HIV
Thrombo- infxn
cytopenia - due to both decreased
production & increased
b/d

CD4 & CXCR4 (R & co-

R) present on
megakaryocytes - allows
infxn w/ HIV -->
infected cells undergo
apoptosis = dec plt
production

B Cell dysfx in HIV: also

may prod autoAbs vs.
HUS Most  b/dcaused by
plts = often Primarily occurs in Plasma
(Hemolytic endothelial damage due kids exchange
Uremic to Shiga-like toxin of <10 years old (&
Syndrome) O157:H7 serotype of E. elderly) (steroids)
coli
A few days after
episode of bloody
diarrhea, see:

Clinical Triad:
Thrombocytopenia
MAHA
Renal failure
Disease & Def Patho/Mech Clinical S/S Dx/ Tests/Labs Tx Notes
TTP Acquired or genetic Clinical pentad: PC  *Plasma Enhanced by other
(Thrombotic deficiency in vWF- Fever BT:  exchange factors that
Thrombo- metalloprotease Thrombocytopenia (removes damage
cytopenic "ADAMS13" in endo Renal failure PB: shistocytes & helmet autoAbs & endothelial cells
Purpura) cells --> multimers of CNS deficits cells provides (e.g., ticlopidine,
vWF accum -> promote MAHA w/ functional clopidogrel,
plt activation & schistocytes & ADAMS13) cyclosporine, oral
aggregation helmet cells contraceptives;
hypertension,
Excess plt (+)ation -> plt Occurs in adult postpartum)
derived hyaline females
microaggregates in Mortality rate: 10-
microvasc 20%

Microthrombi --> TTP/HUS: platelet

MAHA + organ dysfx, consumption +
w/ consumption of plts = hemolytic anemia
thrombocytopenia w/ shistocytes

Bernard- AR; due to defective plt thrombocytopenia PC: decreased B.S. = Binding
Soulier Dz adhesion to subendo giant plts BT: increased Site issue
matrix lifelong bleeding PFA: abn (increased
problem closure time) +
Inherited defect in PAggTest: abn thrombocytopenia
protien GpIb(-IX cmplx)
= defective plt plug
formation (and
aggregation)
Glanzmann's AR, defective plt lifelong bleeding PC: nml G = Grouping,
thrombastheni aggregation problem BT: increased Gathering
a PFA: increased problem
Inherited defect/absence PltAggTest: abn
of GpIIb-IIIa nml plt count
Storage pool defective rls of certain Numerous, varies w/
disorders mediators of plt dz (beyond our
aggregation, such as scope)
ADP & TXA2
Acquired Aspirin: irreversible Herbal: Uremia:
defects in plt inhibitor of COX Ginseng, Ginko, acquired defect in plt
fx: NSAIDS: reversible Ginger, Garlic: adhesion, secretion &
inhib interact w/ warfarin aggregation -->
& inhibit plts PC: nml BT: 
PT: nml aPTT: nml
Disease & Def Patho/Mech Clinical S/S Dx/ Tests/Labs Tx Notes
Von AD (most; TIII = AR) plt and coag defect Lab findings in Type I: Desmopressi Type O blood:
Willebrand's (but clinical features BT:  (& PFA) n acetate, 25% less vWF vs.
Dz (vWD) Quantitative defect=  primarily of plt PC: nml OCPs in other blood types
vWF: defect) PT: nml women
Type I: 70-80%, mild dz PTT:  vWD: AD, MC
Type III: AR, near a) Epistaxis & Factor VIII (enzymatic): - desamino- hereditary coag
absent, severe dz spontaneous  D-arginine disorder (1% of
bleeding from vWF Ag:  vasopressin population)
Qualitative defect (= nml mucous mbs; vWF:Rcof plt aggreg: (DDAVP):
lvls) petechiae negative increases vWD associations:
Type II: 10-20%; mild- b) Excessive Electrophoresis: vWF lvls MVP, Marfan
mod blding bleeding from nml mutimeric pattern synd,
IIA: 75% of TII wounds -fVIII w/ angiodysplasia
c) Menorrhagia 1) Ristocetin cofactor vWF
vWF Fxns: - dx w/ heavy platelet aggregation (if DDAVP vWD: plt & coag
*1. Bridge betw collagen menses in post- (vWF:Rcof): ineffective) dz
and Gpb1= plt adhesion pubertal female = measure of vWF
(dz = dec plt plug function; Ristocetin = in pregnancy: vWD:
formation) - often unnoticed tetracycline AB; binds to monitor fVIII  PTT, BT
until episode of plts & (+)s vWF Rs levels (will  VIII:c, vWF
*2. Carrier P for factor hemostatic stress (Gpb1) --> leads to plt increase in BT, despite nml
VIII (dental procedure, aggregation if vWF is preg) PC
(dz = coagulopathy) surgery) avail to form bridges betw
- t1/2 fVIII w/ vWF: 12 plts Rx vWD:
hrs - clinical - degree of aggregation = desmopressin
-t1/2 fVIII w/out: 2 hrs presentation varies measure of vWF activity acetate, OCP
widely & many diff
Produced at endo cells & mutations can cause 2) vWF antigen:
megakaryocytes (plts) detects amount of vWF

3) Multimer studies:
electrophoresis to
determine type of dz (TI,
Causes of deficiency: easy bruising II, or III) PT and PTT
Prolonged Acquired
1. Decreased syn of Vit prolonged PT &
K by colonic bacteria aPTT: prob @
-newborns req VitK final common
supplement betw days 2- pthwy, Vit K Ps,
5 meds (coumadin),
2. Decreased reabs at SI liver dz
(w/ fat malabsorption dz)
3. Dec activation of Vit
K by epoxide reductase
@ liver
- Warfarin inhibits
reductase
-Cirrhosis = dec (+)ation
vit K & syn VitK factors
Disease & Def Patho/Mech Clinical S/S Dx/ Tests/Labs Tx Notes
Hemophilia A XLR PC: nml rx as needed MC hereditary dz
(Factor VIII (m) in factor VIII a) Easy bruising & PT: nml assoc w/ life
deficiency) massive hemorrhage PTT: prolonged 1) FFP threatening
Extrinsic pthwy defect--> after trauma or PFA: nml (contains F8) bleeding
decreased generation of operative procedures
thrombin: b) "spontaneous" 2) 30% new (m)- no
a) unable to form stable hem in trauma-prone Cryoprecipita fam hx
clot in response to injury areas te (subset of (m)s same as beta
b) inappropriate c) hemarthroses FFP) thal
fibrinolysis (thrombin - w/ recurrent blding
nmlly regulates) into jt, causes 3)
crippling deformity Recombinant
Level of activity (destroys articular fVIII ($$$)
correlates w/ dz severity: cartilage)
6-50% active: mild dz d) deep muscle 4)
2-5%: moderate; hemorrhage experimental
<1%: severe gene therapy
- tendency to bleed w/ adeno v.
VIII = essential cofactor at joints, muscles &
of IX, req to (+) X CNS 5) stim fibrin
clot
petechieae formation w/
characteristically extrinsic
absent pthwy…

- many
hemophiliacs
contracted
HIV from
repeated
transfusions
Hemophilia B XLR Indistinguishable PT: nml Infusions of FIX present but
(Christmas Variable clinical severity from FVIII defic, but PTT: prolonged recombinant non-fxional in
Dz, Factor IX usu less severe FIX 15%
deficiency) dx of Christmas dz is only
possible by assay of factor
levels

Factor XI Autosomal Indistinguishable Check for if VIII & IX are

defic from FVIII nml
Disease & Def Patho/Mech Clinical S/S Dx/ Tests/Labs Tx Notes
DIC Mech: Variable; common PT: prolonged Remove or tx TNF- DIC in
1. Widespread deposition patterns: PTT: prolonged cause sepsis
of fibrin microthrombi @ 1) Microangiopathic PC: decreased -induces
microvasc --> ischemia hemolytic anemia Fibrinogen: decreased expression of TF
of O2 sens tissues & 2) dyspnea, D dimer: increased -reduces
microangiopathic cyanosis, resp failure expression of
hemolytic anemia (as 3) convulsions & thrombomodulin
RBCs squeeze thru coma --> pro-
narrowed vessels) 4) oliguria & ARF coagulation
2. Use up plts, factors + 5) sudden or - increases
(+) plasminogen = hem progressive expression of
diathesis circulatory failure & adhesion molec at
shock endo cells = inc
2 Major Etiologies: WBC bind and rls
1) Rls of tissue factor or Acute DIC (a/w ROS
thromboplastic obstetric comp &
substances into major trauma): (Lipid A at LPS
circulation dominated by stimulates rls of
- obstetric tissue bleeding diathesis TNF & IL-1)
-massive trauma,
extensive surgery, severe Chronic DIC (a/w AdenoCA: mucus
burns cancer): thrombotic rlsed can directly
-cplasmic granules in complications activate factor X
acute promyelocytic
leukemia Microthrombi most Plasmin: b/d fibrin
- mucus rlsed from often at: brain> and factors V &
adenoCA (MC = lung, heart> lungs> VIII
panc, colon, stomach) kidneys> adrenals>
spleen> liver Fibrin degredation
2)Widesprd injury to products: inhibit
endo cells Kidneys: plt agg, fibrin
-injury that exposes sub- microinfarcts, bilat polymerization &
endo collagen cortical necrosis thrombin
- sepsis (direct injury &
TNF) Lung: hyaline mbs
-immune complexes (reminiscent of
(SLE) ARDS)
-extreme temps (burns,
heat stroke) Adrenals: fibrin
-microorganisms thrombi cause
(meningococci, massive hem in
rickettsiae) Waterhous-Freid
synd
MC due to: obstetric
complicaitons (50%), Sheehan postpartum
malignant neoplasms pituitary necrosis
(33%), sepsis, major
trauma
 Disease & Def Patho/Mech Clinical S/S Dx/ Tests/Labs Tx Notes
Thymic absence/ severe lack of T Tetany Thymus & parathyroids
Aplasia, cells & cell-mediated (hypocalcemia) fail to develop-->
Hypoplasia: immunity Recurrent decreased T cells,
DiGeorge a/w failed develop of viral/fungal infxns decreased PTH,
synd parathyroids (T-cell deficiency) decreased Ca
22q11 deletion: failure to Congenital heart & -absent thymic shadow on
develop 3rd & 4th great vessel defects CXR
pharyngeal pouches

Thymic a/w myasthenia gravis

Thymus

hyperplasia AI: Ab vs. AchR @ NMJ

Thymomas benign or malignant

a/w pure red cell aplasia

Mediastinal 4 Ts:
tumors Thymomas
Teratomas
Terrible Lymphoma
Thyroid
 _x000D_Review of Normal Hemostsais_x000D_

Small vessel 1. Vascular phase: 2. Platelet phase: 3. Coagulation phase: 4. Fibrinolytic phase:
hemostasis a. transient vC a. adhesion a. fibrinogen bound a. Plasmin cleaves insoluble fibrin
response to b. FVII locally (+) b. Plt rls rxn GpIIb/IIIa converted monomers holding plts together
injury by TF c. Plt syn & rls TXA2 to fibrin by thrombin
c. exposed collagen d. Temporary plt plug stops b. forms stable plt
(+)s FXII blding plug

Primary 1. Adhesion: 2. Secretion: 3. Aggregation: Ticlopidine, clopidogrel, Plt surface ppl

Hemostasis: Platelet binds a) alpha granules: secrete plt-plt adherence via abciximab: interfere with GpIIb- ("Plt factor 3"-
-formation of subendo collagen via fibrinogen (FI), fibronectin fibrinogen bridge betw IIIa receptor function PF3): substrate
plt plug w/ Gp1b binding vWF (FXIII), FV, FVIII, & vWF plt GpIIb/IIIa Rs required for clot
vessel injury b) dense bodies: w/ Important platelet storage formation
-ADP: helps plts adhere to proteins: ADP, vWF, fibrinogen
vWF: syn at Wiebel- endothelium (makes sticky) = temporary plt plug: PF4: heparin
Palade bodies in -Ca: binding agent for Vit K only held by Platelet function: stabilizes neutralizing factor,
endo cells dependent factors fibrinogen (no fibrin) intercellular adherens junctions in w/in alpha granules
c) TXA2 generation via COX venular endothelial cells (plt dysfx-
vWF binds VIII and --> vC & plt aggreg. > RBC leakage --> peticheae)
prevents d) conformational change -->
degredation; more ppl exposed at plt PDGF: stimulates sm m cell
decreased vWF= surface hyperplasia, important in
decreased VIII pathogeneisis of atherosclerosis

Secondary Extrinsic system: Intrinsic system: XII, XI, IX, Final common pthwy: Extrinsic system: factor VII Vitamin K-
hemostasis: factor VII VIII X, V, II, I - eval w/ PT dependent factors:
formation of (II- thrombin) procoagulants II,
fibrin clot - activated by tissue (+) X via form cmplx: (I- fibrinogen) Intrinsic system: factors XII, XI, IX, VII, IX, X;
factor IXa, VIIIa, Ca2+, PF3 (plt ppl) VIII anticoagulants
(thromboplastin, (+) thrombin via form - eval w/ PTT protein C and S
FIII) -contact imp for (+) of pthwy cmplx:
in lab; in real life, likely Xa, Va, Ca2+, PF3 Factor XIIa: activates the Vitamin K: liver
(+) X via cmplx: activated by: TF-VIIa kininogen system activated by
VIIa + tissue factor (extrinsic) --> (+) IX epoxide reductase;
Thrombin cleaves Final common pathway: factors X, γ-carboxylates
IXa + VIIIa ((+) by IIa) --> fibrinogen to fibrin & V, II, I factors --> able to
(+)X activates FXIII bind Ca & plt ppl
Factor XIII: cross-links insoluble (PF3)
FXIII: polymerizes & fibrin monomers
Factor XII (Hageman factor) cross links fibrin Calcium: binds γ-
links fibrinolytic system, monomer = solid carboxylated
coagulation system, fibrin plug vitamin K-
complement system & kinin dependent factors
system

XIIa (+)ated by exposed

subendo collagen, HMWK, &
contact factors
 _x000D_Review of Normal Hemostsais_x000D_

Anti-platelet PGI2 (prostacyclin), Aspirin/NSAIDs: Plavix: acts at note:

mechanisms NO: inhibit formation of TXA2 GpIIb/IIIa Rs to factors at serum: II, VII, IX, X
-vD & inhibit inhibit aggregation Barium sulfate plasma: I, V, VIII,
aggregation XIII
- secreted by nml
endothelium (serum - supranate formed after
centrifuge sol'n containing clot;
lacks factors consumed in clot)
Anti- Anti-thrombin III: Thrombomodulin: note: Thrombin fxs: How to keep clotting localized?
coagulation -(+) by heparin-like 1. modulates thrombin (pro-fibrin)
molecule 2. activates Protein C 1) locally augments When swept away from injury site,
- inactivates II fibrin deposition via thrombin inactivated by
(thrombin), Xa & (+) Protein C inactivates (+)ation of intrinsic thrombomodulin which also leads
IXa FV & FVIII pthwy to (+) of Protein C
- estrogen (birth -APC inhibs V & VIII
control) inhibits = 2) augments factors -other factors removed at liver
pro-coagulant that inhibit fibrinolysis
Fibrinolytic Activation of Control of Fibrinolysis: Plasmin b/d fibrin, Alteplase & reteplase =
system plasminogen by: 1. alpha2 plasmin inhibitor produces fibrin split recombinant tPA
(b/d of fibrin -tPA (binds and inhibits plasmin) producs (A, B, D)
by plasmin) -Urokinase-like PA other activators of plasminogen:
(urokinase from 2. plasminogen activator D split products = "D factor XIIa, Streptokinase,
human urine) inhibitor (inhibits tPA) dimers" = cross linked Anistreplase
fibrin monomers
Aminocaproic acid: inbibits
plasminogen
Thrombosis: Perfect storm of: Endothelial injury: Hypercoag state: Venous stasis:
1. Endothelial injury -turbulent flow at arterial -genetic: APCR, nml small amount of spontaneous
2. Abn blood flow bifurcation, area of plaque, increased factor activation doesn't get diluted
(stasis) cig smoke --> arterial thrombi homocysteine, and swept away by blood flow
3. Hypercoagulable increased prothrombin -form just upstream of valves,
states propogate in direction of flow

Nonthromboc Small hemorrhages Platelet count,

ytopenic (peticheae & bleeding time, PT &
purpuras: purpura) at skin or PTT:
mucous mbs, esp the ALL normal
gingiva
Infxn: Henoch-Schonlein purpura: Scurvy, Ehlers- Hereditary hemorrhagic Perivascular
Meningococcemia, systemic HS dz, unknown Danlos, Cushing's dz: telangiectasia (Osler Weber Rendu) amyloidosis:
septicemia, cause; weaken vessel walls AD; dilated, tortuous vessels w/ weakens vessel
endocarditis, Purpuric rash, colicky abd thin walls, readily bleed --> MC walls = bleeding;
rickettsial dz; pain, polyarthralgia, acute GN under mucous mbs of nose MC seen w/
vasculitis & DIC - all due to IC deposition (epistaxis), tongue, mouth, eyes, amyloid light chain
through GI tract amyloidosis
Drugs: IC HS
vasculitis
 _x000D_Review of Normal Hemostsais_x000D_

Deficiency Vit alcoholism prolonged PT and

K dependent PTT (b/c factors
proteins invovled in both
pthwys)
Tx of DVT w/ PE: O2 + cardiac Unfractionated heparin, Heparin: meas PTT Heparin: advantage = reversible w/
& pulm support + to INR at 2-2.5 protamine
heparin - LMWH: does not affect PTT Coumadin: meas PT
w/out: heparin (dose based on pt weight) Coumadin:
-protamine doesn't fully (both PT & PTT reverse w/ vit K but takes 6-8hrs
reverse LMWH prolonged in both Proteins C & S also drop
-gradually wean from heparin, drugs, but since fVII -CAN clot on coumadin, especially
place on Coumadin (INR: rebounds fast, use PT at beginning of tx!! Proteins C & S
betw 2-3) to follow coumadin) drop 1st = hypercoagulable in pts
-APS: tx pt to INR > 3 (only who are deficient in Protein C (htz
case where tx to INR >3!) included)
-also poss skin necrosis