259. Acquired Coagulation Disorders

Question 1

What are four key processes that can lead to pathologic bleeding or thrombosis?

Answer 1

1. Vascular Integrity
2. Platelet Function (Qualitative, Quantitative)
3. Clotting Proteins/Coagulation
4. Fibrinolysis

Question 2

VITAMIN K DEFICIENCY

• what is the significance in coagulation?
• where does it take effect?
• sources in diet
• causes (3)
• what patient population is especially at risk? why?
• tx

Answer 2

K: cofactor in gamma carboxylation of Factors 2, 7, 9, 10 (anti-coagulation) and Protein C, S (pro-coagulants) in the liver
Diet: Leafy green vegetables, activated by intestinal flora, fat soluble absorption via bile acids in terminal ileum
Causes: severe malnutrition (NPO), chronic ABx use (less absorption/activation), malabsorption syndromes

NEWBORN: at risk of bleeding due to lack of gut microbiome, can present as GI bleeding and progress to ICH, all babies given vit K IV as prevention (needed more than oral because oral not as good)

Tx:
No overt bleeds = Oral vit K (SC vit K if malabsoprtion/NPO - cant absorb via gut)
Overt Bleed = IV Vit K (rapid reversal, risk anaphylaxis), Plasma products (FFP, PCC) to correct bleeding

Question 3

COAGULOPATHY OF LIVER DISEASE

• 4 coag functions of normal liver
• changes that favor bleeding (7) and favor thrombosis (4)
• tx of liver disease coagulopathy

Answer 3

Normal fx: synthesize clotting factors, synthesize coag inhibitors (ATIII), TPO synthesis, clearance of activated hemostatic proteins and inhibitor complexes from circulation

Favor Bleeding

1. Decreased clotting factor synthesis (2, 5, 7, 9, 10, 11)
2. Decreased fibrinolytic inhibitors (TAFI)
3. Qualitative and Quantitative fibrinogen defects
4. Imbalanced increase in tPA relative to smaller increase in PAI-1 (more fibrinolysis than clotting)
5. Thrombocytopenia (less TPO)
6. Abnormalities in platelet aggregation
7. NO and PGI2-mediated platelet inhibition (qualitative platelet defect)

Favor Thrombosis

1. Increase vWF, F8 (extrahepatic synthesis)
2. Decreased plasminogen
3. Decreased anticoagulants: ATIII, Protein C, Protein S, alpha-2 macroglobulin
4. Decreased heparin co-factor II

TX: DO NOT CONSIDER PTS as “auto-anticoagulated” bc can clot AND bleed at same time

• DO NOT TX LAB VALUES
• Use blood products when clinical signs: active bleeding, invasive procedures: Platelets, FFP (all clotting factors and anticoagulants), Cryoprecipitate (F8, 13, Fibrinogen, vWF), Vitamin K

Question 4

DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

• what is it
• Pathophys (3 key features)
• Acute vs Chronic
• Causes (4)
• Dx
• Tx

Answer 4

DIC: systemic process involving thrombosis + hemorrhage, exposure to procoagulants, circulating fibrin with fibrinolysis, depletion of clotting factors + platelets = END ORGAN DAMAGE
PPhys: Activated Coag by trigger
1. Bleeding Diathesis: via platelet/clotting factor consumption, fibrinolysis (high fibrin degradation products - interfere with fibrin polymerization, binds GPIIB/IIIA)
2. Microangiopathic HA via fibrin deposition
3. Ischemia w/ Organ Damage via thrombosis/fibrin deposition

Acute: decompensated intravascular coagulation, depletion of platelets, clotting factors, FDP generation, Clinical: BLEEDING (+ MAHA)

• AKI due to microthrombi (ischemia) and hypotension
• Pulm Hemorrhage/ARDS
• CNS Hemorrhage
• Hyperbilirubinemia (due to MAHA, liver dysfx/shock to liver)

Chronic: liver and bone marrow compensate for clotting factor and platelet loss, Clinical: THROMBOTIC (consider malignancy - most common cause)

Causes: 1. Infection/Sepsis (Shock = low blood flow = tissue damage)

2. Tissue Damage (surgery/trauma = release of tissue enzymes and PLs from damaged tissue)
3. Cancer (TF expression by circulating tumor cells = procoagulant)
4. Obstetrical complications (amniotic fluid emoblus, abruptio placenta = release of thromboplastin-like material)

Dx: clinical, thrombocytopenia (<100K), FDP + D-Dimer elevations, prolonged PT/PTT, low fibrinogen (increases TT)

TX: treat underlying cause (sepsis, trauma, malignancy), blood product support only if active bleeding AND…(platelets if thrombocytopenic, FFP if elevated PT/PTT, fibrinogen/cryoprecipitate if low fibrinogen)

Question 5

ACQUIRED FVIII INHIBITOR

• cause (2)
• what it is
• symptoms
• labs
• tx
• prognosis

Answer 5

Cause: alloantibody in congenital Hemophilia A or autoAb development (post-partum, with immunologic disorder, malignancy related, 50% IDIOPATHIC)

• IgG specific to F8 (no interference with vWF)
• sx: easy bruising, bleeding, large muscle hematoma (hemarthroses rare), GI/GU bleeding
• labs: low F8 activity, prolonged PTT with NO CORRECTION on mixing study (may initially shorten, then prolong as Ab has time to dilute)
• labs: quantify Ab titer with BETHESDA ASSAY (BU)

Tx:

• low titer: DDAVP, F8 concentrate (overwhelm inhibitor)
• high titer: PCC, recombinant F7a (bypass inhibitor pathway)
• eradicate antibody: immunosuppressives (steroids, cytoxan), RITUXIMAB

Prognosis: 1/3 spontaneously resolve, 20% relapse, need eval for malignancy, autoimmune condition, other precipitating factor

Question 6

Antiphospholipid Syndrome (APLS)

• what it is
• labs
• pphys
• CM
• dx
• tx

Answer 6

AutoAbs against anionic PL and plasma proteins (Lupus anticoagulant - LAC, anticardiolipin Ab, anti-beta-2-glycoprotein)

• LAC causes elevated PTT (but no bleeding risk, increased risk of THROMBOSIS)
• PPhys: Abs alter interplay between endothelial cells, monocytes, platelets, complement = increase tissue factor, TxA2, complement activation = procoagulant state
• Second Hit: other CV risk factors, tobacco, E tx may lead to clinical thrombosis

CM: Venous Thrombosis (high recurrence), Arterial Thrombosis (ischemia/infarction, TIA/stroke >50% cases, >20% involve coronary vessels), Adverse Pregnancy Outcomes (miscarriage, preterm birth, preeclampsia, IUGR), some thrombocytopenia, hemolytic anemia, livedo reticularis

May be transiently detected in infection, cancer, medications (procainamite, chlorpromazine) = NEED TO RETEST

Lupus Anticoagulant: elevated PTT, NO CORRECTION ON MIXING, causes THROMBOSIS

Dx: 1 clinical (thrombosis, pregnancy comp) + 1 lab criteria (LAC, anticardiolipin, anti-beta-2-glycoprotein)

Tx:
Venous thrombosis - Anticoagulation
Arterial Thrombosis - Antiplatelets and/or Anticoagulation
Pregnancy - Anticoagulation with ASA
Catastrophic anti-PL Ab Syndrome: Plasma exchange to lower Ab load (life threatening involvement of 3 organs thrombosed)