Note:  The test will be May 6, 4-6 pm in SON G013 (auditorium).  Please let me know if this is going to cause any problems.  Because I only have 3 lecture periods, I am including thyroid hormones with today's lecture. Please pull up the lecture notes for Lecture 12. Thyroid is the first part.

Coagulation

Objectives:

1. List the factors necessary for successful coagulation.

2. What activates the extrinsic and intrinsic pathways?

3. What processes are involved in fibrinolysis?

4. What factors are considered when evaluating coagulation?

5. Identify critical values for platelets, activated partial thromboplastin time, prothrombin time and INR.

6. Define thrombocytosis, thrombocytopenia

7.  

Stages of Coagulation

• Injury

• Platelet adhesion

• Platelet aggregation

• Fibrin formation

• Fibrin dissolution

• Injury healed

Coagulation Cascade  http://www.medinfo.ufl.edu/year2/coag/physcasc.html

Contact with foreign substance → XII → XI → VIII  
                                                                          ↓ 
             fibrinogen (I)    ←     II    ←    V    ←    X
                    ↓                       ↓                         ↓
               fibrin         ←         XIII                       VII       
                     ↓                                                  ↑
                  clot                      tissue damage →  III

Clot Formation

• Fibrinogen → fibrin (thrombin involved)

• Fibrin stabilizing factor (transglutaminase [XIII]) - activated by thrombin and calcium

• Plasminogen → plasmin

• Plasmin starts fibrinolysis

• Plasmin inactivated immediately after dissolving clot

Regulation of coagulation   http://www.medinfo.ufl.edu/year2/coag/regulate.html

• Intact endothelium secretes prostaglandin 12 - prevents platelet activation and causes vasodilation

• Antithombin III - protease inhibitor

• Protein C - inactivates V and VIII

• Extrinsic pathway inhibitor

• Damaged cell release plasminogen activator

Failure of coagulation regulation

• Antithombin III deficiency
• Protein C deficiency
• Protein S deficiency
• Inherited resistance of Factor Va to cleavage by activated Protein C

Tests

• Specific protein assays
• Factor V susceptibility test

Fibrinolysis

• Tissue plasminogen activator and urokinase released at time of injury
• Plasminogen → plasmin
• Plasmin degrades fibrin to D-dimers and fibrin degradation products (FDP) and degrades V, VII and GP1b
• Subendothelium activates XII, kallikrein released - activates plasmin, releases bradykinin

Assessing Coagulation

• Immediate clinical history
  • Massive transfusions
  • Bleeding from IV sites, surgical sites
  • Consider dilution or consumption
  • Cardiopulmonary bypass
• Personal history
  • Family history
  • History of triggering event
  • Frequency of abnormal bleeding
  • Duration of abnormal bleeding
  • Location of abnormal bleeding
  • Medical diseases
    • Liver
    • Renal
    • Hematology
    • Vitamin K deficiency
    • Vitamin C deficiency
    • Solid organ malignancy (prostate, lung, colon)
  • Medications
    • Aspirin
    • Ibuprofen
    • Coumadin
    • Heparin

LAB TESTS

Platelet Count

• Normal 150,000 - 450,000
• Important values
  • < 60,000 - bleeding problems
  • < 20,000 - spontaneous bleeding
  • > 1,000,000 - increased  viscosity
• Specimens stored > 24 hours increases aggregation
• Automatated counters
  • Hemolyzed RBCs counted as platelets
  • Bacteria counted as platelets
• Manufactured in bone marrow
• Life span - 7 days
• Impaired aggregation
  • Aspirin permanent during lifespan of platelet
  • NSAID decreased only while taking drug
• Spleen is scavenger

Thrombocytosis

• Malignancy
• Polycythemia vera
• Hemorrhage
• After surgery
• Iron deficiency
• Chronic inflammatory diseases
• Hodgkin's disease
• Chronic myelogenous leukemia

Thrombocytopenia 

• Increased destruction by immune factors
  • Sepsis/DIC
  • Drugs
  • Post-transfusion
  • Heparin induced
• Increased destruction, nonimmune - Thrombotic microangiopathies 
  • Anemia
  • Renal insufficiency
  • Fever
• DIC
• Dilution
• Sequestration
• Decreased production
  • Leukemia
  • Metatastic cancer
  • Drugs - alcohol, thiazides, HIV drugs
  • Splenomegaly - including CHF and respiratory failure

Diagnosis

• Petechiae on skin and mucous membranes
• Platelet count

Treatment

• If autoantibody caused, give steroids or gamma globulin
• Splenectomy
• Platelet transfusions - 1 platelet pack should increase platelet count by 5,000-10,000

Platelet Function Tests

• Have adequate platelets, but they don't work
  • Drugs
    • Aspirin
    • Ketorolac
    • Beta-lactam antibiotics - penicillin, ticarcillin
  • Uremia
  • HIV
  • DIC
  • Liver disease - decreased factor synthesis
• Platelet aggregation - add agonist 
  • Expect to see reversible aggregation
  • Followed by irreversible aggregation (platelets disintegrate)
• Heparin induced platelet aggregation - used to diagnose heparin induced thrombocytopenia
• Hess test - inflate sphygmomanometer between SBP and DBP for 10 minutes. Release and count number of petechiae in 5 cm circle. Normal is < 15.  Used to assess problems with vascular endothelium, and platelet adhesion and aggregation.

Prothrombin Time (PT)

• Normal 10-13 seconds
• Measure both patient and control
• Results influenced by sensitivity of thromboplastin reagent
• Can't compare PT values between different labs, because use of different reagents
• Need to look at INR (International Normalized Ratio)

Increased PT

• Decreased production of prothrombin
  • Unpaired liver production
  • Coumadin therapy
• Inability to absorb vitamin K
• Prolonged antibiotic therapy
• Neonates - inadequate function of some clotting factors & absence of GI bacteria to make vitamin K

INR (International Normalized Ratio)

• Must be on coumadin for 4 days before INR level is stable
• Prolonged INR
  • Coumadin
  • Vitamin K deficiency
  • Severe liver disease
  • Massive blood transfusions
  • DIC
  • High dose heparin
• Recommended INR
  • 2-3 for DVT, pulmonary emboli, MI, tissue heart valve, valvular heart disease, atrial fibrillation
  • 3-3.5 for cardiogenic emboli, mechanical heart valve

Treatment of high INR

Activated Partial Thromboplastin Time

• Normal  25040 seconds
• Measures non-Vitamin K dependent factors
• Use to monitor heparin therapy
• Abnormal in liver disease
• Goal:  1.5-2 times normal
• Prolonged APTT
  • Heparin therapy
  • Hemophilia
  • Massive blood transfusions
  • High dose coumadin therapy
• Decreased APTT
  • Hypercoagulability of pregnancy
  • Possible thrombophlebitis

Activated Clotting Time

• Done at bedside
• Measures all factors
• Is sometimes used instead of APTT
• Major benefit:  it is FAST

Thrombin Time

• Normal < 15 seconds
• Prolonged
  • Heparin Uremia
  • Lupus
  • Hyperbilirubinemia
  • Abnormal fibrinogen
  • Abnormal globulin
  • Fibrin degradation products

Bleeding Time

• Sphygmomanometer inflated to 40 mm Hg
• One or two cuts on volar surface of arm
• Filter paper used to blot edges of wound until bleeding stops
• Normal is 2-9 minutes
• Prolonged
  • Deficiency of von Willebrand factor
  • Platelet deficiency or abnromality - heparin or aspirin
  • Anemia

Fibrinogen

• Normal 160-300 mg/dl
• Measures conversion of fibrinogen to fibrin
• Increased
  • Elderly
  • Infection
  • Hemorrhage
  • Trauma
  • Neoplasm
• Decreased
  • Excessive consumption
  • Decreased production
  • Increased fribrinolysis
  • Congenital deficiency
•  Normal quantity, decreased function
  • Ciongenital dysfibrinogenemia
  • Multiple myeloma

FDP/FSP/D-dimer

• Lysis of fibrin by plasmin or digestion of fibrinogen
• Increased levels
  • Renal disease
  • Hemorrhage
  • Cirrhosis
  • Leukemia
  • Some cancers
  • Interuterine deaths
  • Thromboembolic disorders
  • Extensive vascular clotting

Can assay each individual clotting factor

Tips for patients taking coumadin

• Protection
  • Wear shoes anytime out of bed
  • Use a soft toothbrush
  • Use electric shaver - no razors
•  Education: take medication at same time every day
• Vitamin K in diet can change INR - eat consistent amount of foods high in vitamin K
• Inform health care provider of all medications, including OTC and herbal
• Ask before adding any medications to regime

Care of the patient with hypocoagulability

• Assess medication history for past 10 days
  • Prescription
  • OTC
  • Herbal
• Soft toothbrush
• Electric shaver
• No injections
• Apply pressure for 5 minutes to all punctures, then apply pressure dressing
• Use saline lock for blood draws
• Maintain current IV access
• Examine skin and mucous membranes daily
• BP - inflate cuff 20 mm Hg above last reading, no automatic BP cuffs
• Do not allow out of bed without foot covering
• Patient teaching
  • Reasons for precautions
  • Gentle nose blowing - may use saline or water soluble gel
  • Do not remove scabs or crusts
  • Avoid aspirin, alcohol, salicylates, anti-inflammatories
  • Read all labels on all meds and hygiene products
  • Active bleeding
    • Apply constant pressure for 15 minutes - no peeking
    • Epistaxis - sit upright, pinch nose for at least 10 minutes, if not resolved, go to ED
    • Gingival bleeding - apply direct pressure with dry tea bag

Disorders of excess clotting

• Causes venous and arterial thrombosis
• Venous thrombus cause by disease or injury to leg veins → venous stasis → pulmonary emboli
• Arterial thrombosis caused by athrosclerosis
• Diagnosed by venograms, arteriograms, and ultrasound

Treatment of venous thrombi

• Anticoagulation
• Vena cava filters
• Thrombolytics

Treatment of arterial thrombi

• Angioplasty
• Thrombolytics
• Arthrectomy

Care of the Patient with Hypercoagulability

• Maintain hydration
• Maintain activity
• Check Homan's sign daily
• Regular phlebotomies