4 Hemostasis & Related Disorders Flashcards
Primary Hemostasis
- Transient vasoconstriction of damaged vessel
-Via neural reflex
-Via endothelin (from endothelial cells) - Platelet adhesion to damaged vessel
-vWF binds to exposed collagen
-PLTs bind vWF using GP1b receptor
(vWF from WP bodies of endothelial cells > alpha granules of PLTs)
- Platelet degranulation
-PLTs change shape once adhered
-Release of mediators…
-ADP to promote GP2b/3a receptors on PLTs
-TXA2 to promote PLT aggregation - Platelet aggregation
-GP2b/3a receptors on PLTs linked via fibrinogen
-Forms platelet plug (weak)
Secondary Hemostasis (Coagulation Cascade)
Converts fibrinogen (in PLT plug) to fibrin
Fibrin is then cross-linked
Yielding stable PLT-fibrin thrombus
Coagulation factors are made in liver, hang out in blood until activated
Activation requires…
1. Exposure to activating substance
2. Phospholipid surface (of PLT)
3. Calcium (from PLTs)
Disorders due to factor abnormalities
DEEP bleeding into muscles & joints
Re-bleeding after surgery
Labs
-PT (Extrinsic) Measures Coumadin
-PTT (Intrinsic) Measures Heparin
Disorders of Primary Hemostasis
Due to QUANT/QUAL abnormalities in PLTs
-ITP, MAHA (TTP, HUS)
-Bernard-Soulier, ***
Mucosal & Skin Bleeding
-Epistaxis, hemoptysis, GI bleed, hematuria, menorrhagia, intracranial bleeding!
-Petechiae (QUANT), purpura, ecchymoses
Labs
-PLT count (150k to 400k)
-Bleeding time? (2-7 min)
-Blood smear (#, size)
-Marrow bx (Megakaryocytes)
Immune Thrombocytic Purpura (ITP)
Autoimmune, IgG against PLT antigens (GP2b/3a)
-Auto-ab’s made in spleen
-Bind to PLTs
-Bound product consumed by splenic M0’s
***Most common cause of PLTpenia in kids AND adults
Acute - In kids
-Weeks after viral infxn OR immunization
-Self-limited, resolve in weeks
Chronic - In adults, especially F of reproductive age
-Primary or secondary (Lupus)
-Transient PLTpenia in newborn b/c IgG crosses placenta
Labs
-Low PLTs, < 50k
-Normal PT/PTT (Coagulation Cascade OK)
-High MGK’s
Treatment
-Corticosteroid (Kids respond well, Adults may relapse)
-IVIG (To distract splenic M0’s)
-Splenectomy (To eliminate source of Ab & site of destruction)
Micro-Angiopathic Hemolytic Anemia (MAHA)
Pathologic* formation of PLT (micro)thrombi in small vessels
-RBCs sheared (Shistocytes! “Helmet cell”)
-PLTs consumed in formation of microthrombi
Due to TTP & HUS
-Skin & mucosal bleeding
-Fever
-CNS abnormalities (TTP)
-Renal problems (HUS)
Labs
-Low PLTs with increased bleeding time
-Normal PT/PTT
-Anemia with Shisto’s
-High MGKs
Treatment
-Plasmapheresis & corticosteroids (TTP)
(Microangiopathic = Pathology in small vessels)
Thrombotic Thrombocytopenic Purpura (TTP)
PLT (micro)thrombi form in small vessels BECAUSE decrease in ADAMTS13 enzyme BECAUSE of auto-ab in adult F
ADAMT13 = Chops up vWF to stop hemostasis
-So without it, abnormal PLT adhesion
-Formation of PLT microthrombi
-PLTs get consumed
Hemolytic Uremic Syndrome (HUS)
PLT (micro)thrombi form in small vessels & cause shearing of RBCs
BECAUSE of endothelial damage due to infxn with E. coli O157:H7 & verotoxin (Kids & undercooked beef)
Bernard-Soulier Syndrome VS. Glanzmann Thrombasthenia VS. Aspirin VS. Uremia
Genetic GP1b deficiency, PLT adhesion impaired
Smear with mild PLTpenia , enlarged PLTs
HINT: Enlarged PLTs = “Big Suckers”
Genetic G2b/3a deficiency, PLT aggregation impaired
Aspirin irreversibly inactivates cyclooxygenase & without TXA2, PLT aggregation impaired
Uremia (high blood urea with kidney problems) fucks with adhesion & aggregation
Hemophilia A VS. Hemophilia B (Christmas Disease)
Genetic Factor 8 deficiency, X-Linked, De-novo
+++PTT (Dec Factor 8)
Normal PT
Normal PLT count & bleeding time
Tx. Recombinant Factor 8
Hemophilia B: Same shit but Factor 9
(Autoimmune) Coagulation Factor Inhibitor
Auto-ab, especially against Factor 8
Same labs as Hemophilia A
Mixing Study: Adding in normal plasma (with new Factor 8) does NOT correct this disease, Mixing Study FAILS, because ab’s just keep coming
Von Willebrand Factor Disorder
Autosomal dominant vWF deficiency
Most common inherited coagulation disorder***
+++Bleeding time (Mucosal & skin bleeding)
+++PTT (No vWF to stabilize Factor 8)
Normal PT
Abnormal ristocetin test (PLT do not aggregate)
Tx. Desmopressin (to increase release of vWF from WP bodies of endothelial cells)
Vitamin K Deficiency
(Vit K needed for Factors 2, 7, 9, 10, C, S)
Newborns ~ No GI biome yet
Long-term abx ~ No GI biome
Malabsorption ~ No fat soluble vitamins
Liver Failure Causing Secondary Hemostatic Disorder
(Liver produces many of the coagulation factors & epoxide reductase, which activates vit K)
Monitor with PT
Large-Volume Transfusion Causing Secondary Hemostatic Disorder
(Dilutes coagulation factors, creating relative deficiency)
Heparin Induced Thrombocytopenia (HIT)
PLT destruction secondary to heparin administration
- Heparin forms complex with PLT Factor 4
- IgG auto-ab’s form against this complex
- Destruction of PLTs
Complication: Fragments of destroyed PLTs may activate remaining PLTs, causing thrombosis (So you have low PLT count & clotting all at once)
Tx. Stop heparin
Start other anti-coagulant (NOT Coumadin)
Disseminated Intravascular Coagulation (DIC)
Pathologic activation of cascade causing widespread (micro)thrombi…
-Ischemia & infarct
-Consumption of PLTs
-Bleeding from IV sites, mucosal surfaces
Secondary due to…
-Ob complication
-Sepsis
-Adenocarcinoma
-AML
-Rattlesnake bite
Labs:
Low PLT count
+++PT/PTT
Low fibrinogen (Consumed by microthrombi)
MAHA
+++D-dimer (Fibrin split product) Best test!!!
Tx. Underlying cause
Transfuse blood products
Cryoprecipitate
Disorders of Fibrinolysis
Plasmin normally responsible for shutting down clotting, so if there’s plasmin overactivity…
-Excessive cleavage of fibrin
-Excessive cleavage of fibrinogen
-Excessive cleavage of coagulation factors
-Excessively blocks PLT aggregation
(Plasminogen to Plasmin via tPA!)
Examples:
1. Radical Prostatectomy = Release of urokinase activates plasmin
- Cirrhosis = Decreased production of alpha-2 antiplasmin, which should inactivate plasmin
+++PT/PTT/Bleeding time
Normal PLT count (R/o DIC)
+++Fibrinogen split products (without D-dimer)
Tx. Aminocaproic acid (Blocks activation of plasminogen)
Thrombosis
Pathologic formation of intravascular blood clot in artery OR vein, esp DVT of leg below knee
Lines of Zahn + Attachment to vessel wall
- Would NOT see these in post-mortem clot
Risk of Thrombosis: Disruption of Flow
(Stasis OR turbulent)
-Pt immobilization (Long airplane flight)
-Cardiac wall dysfunction (Afib, post-MI)
-Aneurysm (Blood pools)
Risk of Thrombosis: Endothelial Cell Damage
Endothelial cells…
-Keeps subendothelial collagen covered
-Produces multiple anti-thrombin molecules***
Ex. Atherosclerosis
Vasculitis
High Serum Homocysteine
-Vit B12 or Folate deficiency
-Cystathionine-Beta-Synthase Deficiency
-***
Risk of Thrombosis: Hypercoagulable State
Protein C or S Deficiency
***
Factor V Leiden
-Mutated Factor 5, can’t be deactivated by C/S
-Most common inherited hypercoagulable state
Prothrombin 20210A
-Inherited point mutation in Prothrombin, causing increased expression
Anti-Thrombin-III (AT3) Deficiency
***
Oral Contraceptives (With Estrogen)
***
Embolism
Intravascular mass that travels & occludes downstream vessel
Thromboembolus (>95%)
Atherosclerotic embolus (Cholesterol crystals)
Fat embolus (Soft tissue trauma, fracture)
-Dyspnea & petechiae
Gas embolus (Decompression sickness)
-Joint, musle pain ~ “Bends”
-Resp symptoms ~ “Chokes”
-Chronic disease with multifocal ischemic necrosis of bone ~ Caisson’s
-OR Laparoscopic surgery (Air pumped into abd)
Amniotic fluid embolus
-SQ cells & keratin debris from fetal skin
-Enters maternal circulation during L&D
-Dyspnea, neuro sx’s, DIC***
Pulmonary Embolism
> > > DVT of LE, femoral/iliac/popliteal veins
Clinically silent because dual blood supply & embolus usually small/self-resolves
Complications:
1. In 10%, Pulmonary infarction with obstruction of large/medium artery + Pre-existing cardio-pulmonary compromise
Dyspnea, hemoptysis, pleuritic CP & effusion
V/Q mismatch (Q abnormal)
Spiral CT shows vascular filling defect
Doppler US of LE to identity source
+++D-dimer
Gross: Hemorrhagic (red) wedge-shaped infarct
- Sudden death with “large saddle embolus” that occludes R/L pulmonary arteries, causing electromechanical dissociation
- Emboli that reorganize over time can cause pulmonary HTN
Systemic Embolism
> > > Thromboembolus, most arise in L heart & travel through systemic circulation to occlude flow to organs & LE’s
