• “Blood Thinners” HEMOSTASIS ANTICOAGULANTS ANTITHROMBOTICS BLEEDING DISORDERS

•
• HEMOSTASIS: “STOP BLEEDING”
• PRIMARY HEMOSTASIS: platelet plug of activated platelets (by phospholipids or
fibrinogen) at injury
• SECONDARY HEMOSTASIS: Coagulation Cascade (Tissue Factor Pathways) strengthens
plug with fibrin strands.
• BLOOD CLOT vs. THROMBUS
• Blood clot: one that is formed in a vial or post mortem, the final product of blood
hemostasis.
• Thrombus: is a healthy response to injury, but can be harmful in Thrombosis:
(obstruction of blood flow through healthy blood vessels, ex. Stroke, Pul.Emb., MI)
• Two components to a Thrombus: aggregated platelets (platelet plug) and cross linked
fibrin
• Platelet plug = “White Clot” (before organized)
• Heart Attack/MI caused by Platelet Plug in coronary arteries, a “Coronary Thrombosis”
• ANTITHROMBOTIC DRUGS
• There are two classes of antithrombotic drugs:
• Antiplatelet drugs: Antiplatelet agents prevent platelets from clumping and also
prevent clots from forming and growing.
• Anticoagulants: Anticoagulants slow down clotting, thereby reducing fibrin formation
and preventing clots from forming and growing.
• Antiplatelet Drugs • Antiplatelet Drugs
• Blood platelets are inactive • We now have more potent
until damage to blood vessels drugs, such as: Plavix,
or blood coagulation causes Persantine
them to explode into sticky • No need to test (BT, PFA ) or
irregular cells that clump discontinue Antiplatelet Drugs
together and form a thrombus. before invasive dental
• The first antiplatelet drug was treatment, unless there are
aspirin, signs of a bleeding problem.
• reduces the risk of
heart attack and stroke
.

• PLATELET thrombosis
• In addition to their role in primary hemostasis, activated platelets provide an efficient
catalytic surface for the assembly of the enzyme complexes of the blood coagulation
system, also known as secondary hemostasis.
• Following platelet activation with thrombin, platelet microvesicle phospholipids have a
major role in the initiation of thrombosis.
• PLATELET THROMBOSIS IMPLICATIONS?
• MI: in CORONARY ARTERIES
• ISCHEMIC STROKE: via CAROTID ARTERIES
• VENOUS VERSUS ARTERIAL CIRCULATION
• Arterial the “high pressure” side (systolic) prone to injury from hypertension and
subsequent arteriosclerotic disease plaques (coronary, carotid arteries) prone to
 rupture, that forms platelet clots. Arterial vessels “converge” trapping clots causing
ischemia and tissue death (MI, Ischemic Stroke).
• Venous the “low pressure” side (diastolic), its vessels “diverge” possibly embolizing
clots to travel to form ischemic strokes and pulmonary emboli. Non-embolized clots
form DVTs (deep vein thromboses). Includes heart chambers (A-Fib).
• Development of the AtheroSclerotic Plaque (ASDH)
1. Injury to the vascular endothelium caused by:
o HTN
o High cholesterol
o Immune complexes/viruses
2. Results in Inflammation:
• Macrophages enter the endothelium
• Macrophages accumulate lipid and are called “foam cells”
• Atherosclerotic Plaque:Exposure of Lipid Core causes Thrombus
Problem: Disruption or erosion of the plaque exposes the highly thrombogenic core of the
lipid rich lesion causing platelet aggregation
o Susceptibility of Plaque to disruption
o Depends on Plaque Characteristics such as
a. Shape of the plaque (smooth – jagged)
b. Composition and strength
c. Thickness of fibrous cap
• Therapeutic uses of anti-platelet aggregation drugs include:
• Thrombus Risk Factors: (high cholesterol, high triglycerides, high LDL, sedentary,
• ASHD
• Angina
• MI
• TIAs
• No need to test (BT, PFA ) or discontinue Antiplatelet Drugs before invasive dental
treatment if patient bleeding history is normal and no signs of abnormal bruising.

• “BLOOD THINNERS”
ANTI-THROMBUS/ANTI-COAGULANT THERAPIES
• ASA – anti platelet aggregation, irreversible (off 5-9 days)
• PLAVIX - anti platelet aggregation, irreversible (off 5-9 days)
• COUMADIN-vitamin K antagonist (vitamin K oral or IV)
• NEW DIRECT THROMBIN INHIBITORS:
• for non-valvular A-Fib: dabigatran (Pradaxa), apixaban (Eliquis), rivaroxaban
(Xarelto), and (Lixianae) doxaban directly target the enzymatic activity of
thrombin and factor Xa. no tests, no antedote, patient off drug 24-48 hours
prior to SRP, extractions
• HEPARIN/LOVENOX (low molecular weight heparin) –
• short acting, fast control. activates antithrombin III. Protamine sulfate reverses,
as well as time. Lovenox is a more highly processed product, is useful as it does
not require monitoring of the PTT, more predictable with fewer side effects.
• ENZYMES “Clot Busters” EX.: t-PA, STREPTOKINASE, in ER for acute MI, ischemic stroke
(MRI to diagnose first) vs. hemorrhagic stroke!
• Antithrombotic Therapy
 – Heparin has made bypass surgery and dialysis possible by blocking clotting in external
tubing.
– Warfarin has reduced the risk of the risk of stroke in people with heart irregularities
(atrial fibrillation), blood clots in leg veins (also known as deep-vein thrombosis or DVT),
that can lead to death from pulmonary embolism (a clot that blocks an artery to the
lungs) by more than 70 percent. New DTIs: for non-valvular Atrial Fibrillation
– Aspirin/Plavix has markedly reduced death from heart attacks, and the risk of major
stroke in patients with mini-strokes.
• Anticoagulants: • ANTI-COAGULANT DRUG RISKS
– Anticoagulants slow down – BLEEDING, tests?, reversal
clotting, thereby reducing fibrin drugs? time?
formation and preventing clots – CLOTS/THROMBOSIS, if
from forming and growing. stopped
– COUMADIN – MEDICAL DIAGNOSIS? If
– HEPARIN/LOVENOX mechanical heart valve, -AB
– DIRECT THROMBIN INHIBITORS premedication?
– NO MEDICAL CONSULTATION:
LIABILITY STOPPING THE DRUG,
document if patient stopped the
drug on his/her own!
• COAGULATION CASCADE’S TWO PATHWAYS
– 1) TISSUE FACTOR PATHWAY (primary): strengthens platelet plug with fibrin
(also called Extrinsic Pathway) TEST: PT/INR
– 2) CONTACT ACTIVATION PATHWAY: (clots on negatively charged surfaces: glass,
plastic, metal, etc., ex. Prosthetic heart valves, renal dialysis equipment, heart lung
machines, glass tubes, etc. (also called Intrinsic pathway) TEST: PTT
– Both pathways converge in a final Common Pathway.
• IN VIVO COAGULATION CASCADE
– The classic description of coagulation involved a cascade model consisting of two
distinct pathways:
• The Tissue Factor Pathway (extrinsic pathway)
• contact activation pathway (intrinsic pathway)
– These are now viewed in terms of overlapping phases of initiation, amplification and
propagation (in vivo)
–
• TISSUE FACTOR PATHWAY IN VIVO
– TF-FVII initiates the TF Pathway with a Thrombin burst, but is immediately limited by
TFPI (tissue factor pathway inhibitor)
– TF-FVII Thrombin burst also initiates the Amplification Phase of coagulation
• Amplification Phase of TF Coagulation In Vivo
– Clotting Amplification Factors: FVIII, FIX, FX, FXI, from Contact Activation Pathway.
– For a sustained pro thrombotic continuing coagulation cascade follow up state.
– Example: Hemophilia A (FVIII def.) patient or Hemophilia B(FIX def.) patient with an
injury still continues to bleed with an injury (TF pathway) because of little or no
Amplification Phase of the Tissue Factor Pathway.
• 1ST ANTICOAGULANT DRUGS
– The anticoagulants Heparin and Dicumarol were discovered by chance.
 – Heparin was first discovered in 1916 by a medical student at The Johns Hopkins
University who was investigating a clotting product from extracts of dog liver and heart.
A natural anticoagulant found in mast cells and basophils
– Dicumarol (the precursor to warfarin) in 1939 was extracted by a biochemist at the
University of Wisconsin from moldy clover brought to him by a farmer whose prize bull
had bled to death after eating the moldy clover.
• TEST: Partial Thromboplastin Time (PTT)
– the PTT test evaluates the intrinsic and common pathways (no FVII or FXIII), also it tests
for Heparin range,
– Heparin an IV drug: for dialysis, heart bypass surgery, etc., a hospital use anticoagulant,
short half life, easily controlled. Affects Factors FXa, FII
The typical reference range is between 30-50 seconds (per lab).
• TEST:Prothrombin Time (PT)
– (INR form): The PT test evaluates the extrinsic and common pathways, tests factors I, II
(prothrombin), V, VII, X, a test of coumadin use, liver damage, and vitamin K status;
normal PT/INR is 1, (2-3.5 INR is the therapeutic range for coumadin use)
– A prolonged PT indicates deficiency of 1 or more coagulation factors (I, II, V, VII, or X) or
the presence of a coagulation inhibitor. The PT is not sensitive to deficiencies of
coagulation factors VIII, IX, XI, XII ("intrinsic pathway" factors), nor factor XIII,
• VITAMIN K DEPENDENT FACTORS: II,VII, IX, X
• Anticoagulant Drugs
– Heparin: Test PTT, reversal protamine sulfate, hospital inpatient use
– Lovenox: (low molecular weight Heparin), test: Thrombin Generation Assay, reversal
protamine sulfate, prevent and treat DVT, PE, given as prefilled syringes for SC injection
at home or clinic, no overdoses, testing not needed, consult
– Warfarin: Test PT/INR, reversal Vitamin K (IV, PO)
– NEW ANTITHROMBINS: for non-valvular A-Fib: dabigatran (Pradaxa), apixaban (Eliquis),
rivaroxaban (Xarelto), and (Lixianae) doxaban, directly target the enzymatic activity of
thrombin and factor Xa No Test, no reversal (recently except Pradaxa-”Praxbind”) off
24-48 hours
• NEW CLASS OF ANTI-COAGULANTS
– DIRECT THROMBINS INHIBITORS (FIIa, F10a)(PRADAXA, ELIQUIS, XERELTO, LIXIANAE,
ETC.)
– NO TEST- off 24-48 hours
– NO REVERSAL AGENT (Pradaxa recent exception- proprietary IV reversal agent
“Praxbind” given in the ER)
– POSSIBLE SEVERE BLEEDING PROBLEMS
• Direct Thrombin Inhibitors
– Why not use PT/INR?
• Little to no sensitivity to some Rx and less than optimal to others
• INR can be markedly different depending on reagent used
• THERAPEUTIC USES OF COUMADIN ANTI-COAGULANT
– Atrial Fibrillation – Stroke- Ischemic
– Heart Valves-Prosthetic – Myocardial infarction
– Pulmonary Embolism – Genetic/Acquired Hyper-
– Deep Vein Thrombosis Coagulability (ex,Factor V
– Venous Thromboembolism Leiden
– Congestive Heart Failure
• ATRIAL FIBRILLATION >ATRIAL CLOT RISK
• ATRIAL FIBRILLATION & ISCHEMIC STROKE
1. Blood clot can form during atrial fibrillation
2. Blood clot travels in the bloodstream
3. Blood clot blocks an artery in the brain causing stroke
• COMMON C-V DISEASES
• CAD – Coronary Artery Disease the arteriosclerotic narrowing of the coronary arteries
resulting in decreased blood flow and oxygen to the heart muscle. Risk: MI, Symptoms:
angina, SOB
• CHF – Congestive Heart Failure the heart fails to adequately accept and pump sufficient
blood for normal body needs. Result: congestion (fluid accumulation) of the lungs and
extremities. Risk: MI, Symptoms: SOB, fatigue, swelling of ankles, orthopnea (difficulty
breathing laying flat)
• Assessing your patient • Consultation documentation
• Accurate current medical • HIPAA -respect patient privacy
history law -patient approval signature
• Accurate physical assessment • Written consult from physician
• Accurate medical diagnoses to document-fax convenient
• Avoiding harm, errors, and effective documentation
emergencies for chart
• DENTAL RISK MANAGEMENT • Telephone physician first to
inform of consult, expect fax
form

• Clinical Laboratory Tests: routinely request through patient’s physician

• Hemostasis: BT, PT, PTT, PFA • Serum Electrolytes: Na, K, Cl,
• Complete Blood Count: hct, hb, Bicarb,
wbc, rbc, platelets, • Serum Enzymes
• Differential WBC • Hepatitis-A, B, C, D,
• Serum Chemistry: glucose, BUN, • HIV: CD4 Lymphocyte Level?
creatinine, bilirubin, Ca, Mg, (400)
Phos, • Viral Load? (undetectable)
• Hemostasis: BT, PT, PTT, PFA
• Bleeding Time: tests platelet function, (Ivy method) ear lobe stab/finger tip stab, dab
filter paper Q 30 seconds; normal time: <9 minutes. CBC: Normal platelets: 150,000-
400,000 (75,000 minimum safe for extraction
• -get medical consult)
• Prothrombin Time: (INR form): The PT test evaluates the extrinsic and common
pathways, tests Vitamin K factors (II, VII, IX, X), a test of coumadin use; normal INR is 1,
(2-3.5 INR is the therapeutic range for coumadin use)

• Partial Thromboplastin Time: the PTT test evaluates the contact activation and
common pathways, also it tests for Heparin range, a hospital use anticoaulant. The
typical reference range is between 30-50 seconds (per lab).
 • Platelet Function Assay: The PFA test result is dependent on platelet function, plasma
von Willebrand Factor level, platelet number, a focused platelet test, normal <120
seconds.
• ISI: International Sensitivity Index of Tissue Factor used in the PT/INR
INR = PT patient X ISI
PT control
• PATIENTS ON COUMADIN-WHY?
• Get diagnosis, if prosthetic heart valve, AB premedication a must
• Avoid ASA or Ibuprofen that increases bleeding
• Caution against long term antibiotic use, 3-5 day post-op bleeding from decreased
vitamin K absorption due to loss of normal gut flora
• Patients on antithrombins, ex. Pradaxa, need 24-48 hours off before an invasive
procedure.
• Always have the physician stop the anticoagulant
• WHY IS PATIENT ON COUMADIN RISKS OF REDUCING ANTICOAGULANTS
• Diagnosis? Risk bleeding vs. clotting?
• PT/INR? Therapeutic? (2-3.5)
• Patient on antithrombin (Pradaxa)?
• How invasive is the dental treatment?
• Beware, Some patients take themselves off coumadin.
• Some physicians do also without your consult.
• WHY IS PATIENT ON COUMADIN?
• CAD? • Pulmonary embolism?
• Atrial Fibrillation? 6X risk of • MI?
stroke • DVT?
• Prosthetic heart valve? Needs • Embolism-Stroke?
antibiotic prophylaxis!

• PT-INR THERAPEUTIC RANGE

• 2 TO 3.5 depending on diagnosis
• Never take patient off coumadin! That is practicing medicine, there are risks

• ANTI-COAGULANTS
Warfarin (Coumadin), Heparin/Lovenox
• Used to prevent blood clotting, and emboli formation (ischemic stroke, pulmonary
embolism)
• Atrial fibrillation
• Prosthetic heart valves
• DVTs (Deep Vein thromboses)
• Ischemic Stroke (versus hemorrhagic stroke)
• Pulmonary embolism
• Organ transplants
• ANTI-COAGULANTS
• Warfarin (Coumadin) most commonly used anti-coagulant, requires regular PT/INR
testing and consistent diet re. vitamin K (greens). Vitamin K dependent factors II, VII,
IX, X affected. Antedote: Vitamin K
 • Heparin/Lovenox: fast onset, fine coagulation control, short term transition drug:
renal dialysis, as a hospital inpatient for surgery. Lovenox is low molecular weight
Heparin with fewer side effects.
• Anti-Thrombins (New): Pradaxa, Xeralto, Eliquis; only for non-valvular A-Fib, no test,
no antedote, off 48 hours before invasive dental procedure. Med consult!
• HEPARIN/LOVENOX
• HEPARIN: fast onset, short duration (6h IV) used for renal dialysis (delay dental
extractions to the next day), hospital inpatient for fine control of coagulation.
• LOVENOX: low molecular weight heparin, an interim anti-coagulant – for temporary use
for some out patient surgery (like dental extractions) when coagulation control difficult.
Get medical consult for invasive procedures.
• DRUGS AFFECTING COUMADIN
• ASA, (& NSAIDs) prolongs bleeding (decreases platelet adhesiveness), potentiates coumadin
(inhibits prothrombin synthesis),
• ANTIBIOTICS: can increase PT/INR and bleeding by
reducing GI flora that synthesize vitamin K (coumadin antedote), seen after 4-5 days
or of use
• DRUGS AFFECTING PLATELETS
• ASA: platelet effect irreversible, lasts life of platelet- 5-7 days
• PLAVIX:platelet effect irreversible, lasts life of platelet- 5-7 days
• NSAIDs: platelet effect mild, reversible, dose related, effect gone 24-48 hours.
• NO AFFECT ON PT/INR
• AFFECTS BLEEDING TIME (PLATELETS)
• Prevent or lyse early arterial platelet aggregation thrombi (ex. coronary, carotid)
• “BLOOD THINNING” DRUGS
• PT (prothrombin time) (INR) test required before dental extraction or deep scaling in a
patient on Coumadin (coagulation factor test) unless it was recently performed and is 2-
3.5
• BT (Bleeding Time) may be required if there is concern of platelet function for ASA,
Plavix use (ecchymosis, bleeding).

• Both aspirin and ibuprofen (Motrin) have anti-platelet activity and therefore increase the
likelihood of bleeding following an extraction of a tooth. The anti-platelet activity of Aspirin is
much longer duration than Motrin’s. The anti-platelet activity for ASA is irreversible and
reversed in 5-7 days with generation of new platelets. The anti-platelet activity of ibuprophen
is dose dependent, it is reversed in 24-48 hours when it is discontinued.
Both aspirin and Plavix affect platelet aggregation irreversibly but in different ways.
ASA by COX enzymes, Plavix by ADP effects.

• TESTS FOR HEMOSTASIS

• BT (Bleeding Time): tests platelet function and vessel quality, <9 minutes
• CBC (platelets): 150,000-400,000 platelets normal, minimal 75,000 for “safe” extraction, SRP.
• PT-INR (prothrombin time – international normalization ratio): tests: clotting factors I, II, VII, X,
(tissue factor/common pathways), prolonged in liver disease, coumadin use, factor I, II, VII, X
deficiencies. Not for DTIs!
• PTT (partial thromboplatin time) tests contact activation/ common pathways factors, prolonged
by heparin, levonox, Hemophelia A,B (factors VIII, IX)
• Call physician/hematologist, platelet count? Need “safe” level 75,000 0r more, often 96,000
normal platelet count 150,000-400,000
• Hemophilia A patients (80%) need factor VIII just before procedure. (Hemophilia B needs factor
IX)
• Best to refer to a dentist with hospital privileges like an OMS
• VON WILLEBRAND DISEASE
• Most common hereditary coagulation abnormality described in humans
• It arises from a qualitative or quantitative deficiency of von Willebrand factor (vWF), a
protein required for platelet adhesion.
• Three types of hereditary vWD: vWD Type I(mild-80%), vWD Type II, and vWD III,
present with varying degrees of bleeding tendency, usually in the form of easy bruising,
nosebleeds and bleeding gums,
• vWD Type I is the most common type, typically asymptomatic or may experience mild
symptoms such as nosebleeds.
• Bleeding Time prolonged, PFA abnormal, - vWF
• Medical consult recommended! Tx: Desmopressin Type I releases vWF, for major
surgery, Types II and III Human Factor VIII concentrate also contains vWF
• DESMOPRESSIN? (SYNTHETIC VASOPRESSIN)
• Desmopressin can be used to promote the release of von Willebrand factor in patients
with coagulation disorders such as von Willebrand disease, mild hemophilia A (factor
VIII deficiency), and thrombocytopenia.
• It is not effective in the treatment of hemophelia B (factor IX deficiency) nor severe
hemophelia A