Pathopharmacology

Exam 2 Clotting
Clotting: the process in which blood is converted to a semi-solid gel
Starts in veins and arteries and can move to other places in the body
When clotting doesnt occur, patients are at risk for bleeding
When too much clotting occurs (thrombus), blood flow can be obstructed to major
organs
Excessive Clotting
o Deep Vein Thrombosis (DVT)
o Polycythemia
o Atrial fibrillation: arrhythmia risk for DVT and possibly MI
Causes stasis of blood because atria cannot contract fully, fill fully
Deficient Clotting
o Hemophilia: deficient in one or two of the clotting factors
o Thrombocytopenia
Risk Factors for Clotting
o Age: elderly dont have as much circulation, arent as mobile
o Genetics: hemophilia is a genetic-linked disorder
o Immobility: blood stasis, blood not moving
o Smoking: hypercoagulability
Physiology
o Blood circulates through blood vessels
o Clotting prevents excess blood loss
o Cells and substances maintain a balance of coagulation and anticoagulation
o Tissue damage and platelet activation initiate clotting factors
o Clotting cascade = initiated by the tissue damage and platelet activation,
which mobilize the clotting factors circulating in the blood. Once active,
these clotting factors work with calcium to form fibrin. At this point, blood
coagulation is completed and blood loss stops
Occurs over two pathways, intrinsic and extrinsic, to achieve
hemostasis
Intrinsic = hypoxia, burns
Extrinsic = tissue integrity problem; trauma or even some type
of cancers
Pathophysiology
o Coagulation occurs when blood is slow or impeded
o THROMBUS forms as a result = CAN OBSTRUCT BLOOD FLOW & CAN TRAVEL
Arterial Thrombosis
Venous Thrombosis
Hemostasis: process that, by a series of events, slow blood flow, stop blood loss
at the injury site, and prevents extensive blood loss when the body begins
bleeding
Coagulation: blood aggregation, or clotting
o Disturbances in the coagulation balance cause abnormalities in the bodys
ability to transport blood through the vessels to the cells or to form blood
clots

ARTERIAL
Brings oxygenated blood to
tissue, cells = leads to tissue,
cellular death
MORE SERIOUS!!!
Pain tissue death; lactic acid
(byproduct of metabolism)
Cyanosis of that extremity
Diminished pulse
Cold

VENOUS
Brings deoxygenated blood
back to heart

Swelling
Warmth
Tenderness
Redness

Drugs Affecting Coagulation

Antihemophillic Factor = clotting factor
Heparin = anticoagulant
Enoxaparin = anticoagulant
Warfarin = anticoagulant
Clopidogrel = antiplatelet
Pentoxifylline = hemorheologic drug
Hemophilia: bleeding disorders where there is a deficiency of one of the factors
necessary for clotting
UNCONTROLLABLE BLEEDING
Genetic (X-linked recessive)
Factor VIII deficiency prevalent in males
Factor IX deficiency prevalent in males
Von Willebrand disease prevalent in females
Pathophysiology
o Deficiency of antihemophillic factor (AHF) (aka Factor VIII)
o Produced by the liver and is required to form thromboplastin
o Quantity of AHF determines severity of the disease
o People with hemophilia have 2/3 factors needed for clotting
o People with hemophilia BLEED LONGER, NOT MORE
o Usually picked up in childhood
Clinical Manifestations
o Prolonged bleeding (not more)
o Hemorrhage from trauma
o Excessive bruising not in common places
o SC and IM hemorrhages
o Hemoarthrosis bleeding into joint cavities
o Hematomas
o Spontaneous hematuria blood in urine
o Child may have prolonged bleeding from minor cut, more bleeding
circumcision, bleeding from injections, gums may bleed when brushing teeth
Check history of bleeding, genetic X disorder (mother), child abuse
Diagnostic Evaluation
o History of bleeding

o Evidence of X-linked inheritance

o Lab tests
APPT = activated partial thromboplastin time
Normal range ~30-40 seconds
Therapeutic range ~60-70 seconds
Treatment
o Replacement of missing clotting factors
Pooled plasma
Genetically engineered recombinant
o Depending on source of bleeding
Corticosteroids good for joint pain, inflammation
NSAIDs
Oral -aminocaproic acid (Amicar)
o Prophylactic measures
Infusions of factor VIII
o
Need to treat pain too!
ANTIHEMOPHILIC FACTOR: clotting factors
Pharmacotherapeutics: deficiency of antihemophillic factor A; comes from
pooled human blood
Pharmacokinetics:
o A: IV
o E: not
o HL: 12h
Pharmacodynamics: component of blood clotting required for conversion from
prothrombin to thrombin
Contraindications:
Adverse Effects: same as blood transfusion reactions, hypotension, tachycardia,
allergic reaction
Interactions: none (human blood)
Labs: aPPT, H&H routine blood levels
Patient Teaching: s/s bleeding, storage= refrigeration, only good for 3h after
reconstituted (warmed to room temp), how to draw up concentrate, IV technique
Lifespan Issues: safety has not been established
Deep Vein Thrombosis (DVT): a blood clot formed in one or more of the deep veins,
usually in the legs
May cause leg pain, but may occur without symptoms
Pathophysiology of DVT
o Localized platelet aggregation and fibrin entrap RBCs
o Thrombus enlarges and additional clotting factors attach
o Clot detaches and travels to other places and causes other problems
Ex: pulmonary embolus
o Turbulence of blood flow is the major cause of embolization
Clinical Manifestations of DVT
o Unilateral leg edema (not always)
o Extremity pain (not always)

Feeling of fullness in thigh of calf

Paresthesia sensation of tingling, tickling, pricking, or burning
Warmth
Erythema redness
Temperature
Positive Homans sign takes toes and pulls forward, can have calf pain
Not always good identifier for DVT false positive
DVT Drug Therapy
o Prevention
Low dose LMWH Low Molecular Weight Heparin (given SC)
Warfarin oral
o Treatment
Heparin drip
Warfarin oral
DVT Prevention
o Patient on bed rest should change positions frequently
o Early and aggressive mobilization
o Compression stockings
o Sequential compression devices (SCDs)
o Drug therapy
o Highest risk: surgical pt (post-op)
Thromboembolus: when a portion of a thrombus breaks off and that fragment
travels through the bloodstream and gets lodged in a vessel, occluding blood flow
o When lodged in a coronary vessel, a myocardial infarction (MI) [heart attack]
occurs
o When lodged in the brain, a cerebrovascular accident (CVA) [stroke] occurs
o With decreased blood flow, tissues and cells do not receive necessary oxygen
and nutrients, and necrosis (cell death) occurs
Embolus: (embolism); any undissolved matter carried in a blood or lymph vessel
to another location where it lodges and occludes the vessel
o When lodged in pulmonary vessels, it is called a pulmonary embolus
o
o
o
o
o
o

Anticoagulation Drugs: heparin, enoxaparin, warfarin

KEEP BLOOD FROM CLOTTING, does not work on clots already formed
DO NOT dissolve clots, NOT BLOOD THINNERS
Prevent existing clots from getting bigger and prevents more clots from forming
Works with the body
HEPARIN: anticoagulant
Pharmacotherapeutics: helps to prevent clot development; DVT prevention of
blood clots
Pharmacokinetics:
o A: IV, SC (destroyed by gastric acid)
o E: kidneys
o M: liver, inactivated
o HL: 30-180 min
o Dur: IV 2-6h; SC 8-12h

Pharmacodynamics: rapidly promotes the inactivation of factor X, which in turn

prevents the conversion of prothrombin to thrombin
Contraindications: bleeding disorders, thrombocytopenia
Adverse Effects: bleeding, thrombocytopenia (HIT)
Interactions: ANTAGONIST = protamine sulfate
Labs: aPPT (normal = 30-40sec, therapeutic = 60-70sec) (**drawn every 4-6h),
platelet
Patient Teaching: preventing bleeding/falls, s/s bleeding, warfarin orally when
home, IV pumps
Pregnancy: does not cross placenta or breast milk

ENOXAPARIN: anticoagulant
Pharmacotherapeutics: prevent blood clots; interacts less with platelets; has
predictable response
Pharmacokinetics:
o A: SC
o E: kidneys
o M: liver
o HL: prolonged only need 1/day
Pharmacodynamics: promotes inactivation of factor X, prevents conversion of
prothrombin to thrombin (same as heparin!); interferes with final stage of clotting
cascade
Contraindications: hypersensitivity, pt with prolonged bleeding time
Adverse Effects: bleeding, thrombocytopenia
Labs: no
Patient Teaching: SC aseptic technique, s/s bleeding, activity levels risk of
bleeding
Lifespan Issues: elderly fall risk
Pregnancy: benefits outweigh risks
WARFARIN: anticoagulant
Pharmacotherapeutics: vitamin K antagonist; long term prevention of thrombus
development
Pharmacokinetics:
o A: oral, highly protein-bound
o E: bile, feces
o M: liver, P-450
o Therapeutic Effects: 1-2 days to be therapeutic
Pharmacodynamics: competitively blocks vitamin K at site of action; ANTIDOTE
= VITAMIN K
Contraindications: bleeding disorders
Adverse Effects: bleeding, hemorrhage
Interactions: herbal supplements (ginkgo = increased bleeding risk; St. johns
wart = decreased effectiveness of drug)
Labs: PT, INR (therapeutic 2-3)
Patient Teaching: weekly blood draws, take at night, limit vitamin K intake (green
leafy veggies), avoid alcohol, s/s bleeding
Pregnancy: not recommended

Antiplatelet Drugs: reduce the number of platelets sticking together

CLOPIDOGREL (Plavix): antiplatelet
Pharmacotherapeutics: reduce atherosclerosis (plaque build-up in arteries);
seen in pt who have had MI or heart stent placements
Pharmacokinetics:
o A: GI tract; oral
o E: kidneys, GI tract
o M: liver, protein-bound; PRODRUG; P-450
o Therapeutic effect: 3-7 days to be effective
Pharmacodynamics: inhibits the binding of ADP to its platelet receptor site. As a
result, inhibits platelet aggregation and prolongs bleeding time. Prevents platelets
from sticking together
Contraindications: bleeding disorders, pregnant/breastfeeding
Adverse Effects: NEUTROPENIA, bleeding, GI distress
Interactions: proton-pump inhibitors (Prilosec) = prevents metabolism of drug
(this is prodrug)
Labs: WBC (neutrophils fever), platelet count, H&H
Patient Teaching: s/s bleeding, watch for infection, take with food
Pregnancy: not recommended
Hemorheologic Drugs
Works in arterial system
Peripheral Artery Disease = build-up of plaque in the arteries, lumen gets smaller,
blood flow decreases so tissues/cells do not get oxygen and nutrients
o Pain, coldness, diminished pulses
o Anaerobic metabolism creates lactic acid = PAIN
o Pain increases with activity
PENTOXIFYLLINE: hemorheologic
Pharmacotherapeutics: intermittent claudication for peripheral artery disease
Pharmacokinetics:
o A: GI tract; oral
o E: kidneys
o M: RBCs, liver first-pass effect
o Therapeutic Effect: takes 2-4 weeks to be effective
Pharmacodynamics: increases cAMP levels, decreases platelet aggregations,
promotes vasodilation, decreases blood viscosity
Contraindications: impaired renal function
Adverse Effects: CNS sedation, dizziness, GI upset
Labs: peripheral pulses, base line and progress of drug
Patient Teaching: will take 2-4 weeks to work, know sedative effects, assess
pedal pulses/perfusion, stop smoking, take with food
Lifespan Issues: not recommended for pregnant/breastfeeding; children <18
safety not established
Pregnancy: C; excreted in breast milk

MORPHINE: strong narcotic agonist

Pharmacotherapeutics:
Pharmacokinetics:
o A:
o D:
o E:
o M:
o HL:
o Dur:
o Onset:
Pharmacodynamics:
Contraindications:
Adverse Effects:
Interactions:
Labs:
Patient Teaching:
Lifespan Issues:
Pregnancy: