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Clinical features of bleeding disorders males males

Platelet Coagulatio
disorders n factors
disorders Severity Related to factor level:
Site of bleeding Skin Deep in
mucous soft tissues <1%- Severe -> Spontaneous bleeding
membrane (joints, 1.5%- Moderate bleeding with mild injury
s muscles) 5-25% - Mild Bleeding with surgery or trauma
(epistaxis, Complications Soft tissue bleeding
gum, Hemophilia
vaginal, GI
tract) Clinical manifestations (hemophilia A and B are
Petechiae Yes No indistinguishable)
Ecchymoses Small, Large, Hemarthrosis (most common) -> Fixed joints
(bruises) superficial deep Soft tissues hematomas (e.g muscles) -> Muscle
Hemarthrosis/muscl Extremely Common atrophy, Shortened tendons
e bleeding rare Other sites of bleeding -> Urinary tract, CNC,
Bleeding after cuts Yes No neck (may be life-threatening)
& scratches Prolonged bleeding after surgery or dental
Bleeding after Immediate Delayed (1- extractions
surgery or trauma , usually 2 days)
mild often
severe Treatment of hemophilia A

Intermediate purity plasma products

Coagulation factor disorders Virucidally treated
May contain Willebrand factor
Inherited bleeding Acquired Bleeding
disorders disorders High purity (monoclonal) plasma products
Hemophilia A and B Liver Disease Virucidally treated
Von Willebrands Vitamin K No functional von willebrand factor
disease deficiency/warfarin
overdose Recombinant factor VIII
Other factor DIC Virus free/ No apparent risk
deficiencies No functional von willebrand factor

Dosing guidelines for hemophilia A

Hemophilia A and B
Mild Bleeding
Hemophilia A Hemophilia B Target 80-100% q8-12h; 1-2 days (15U/kg)
Coagulation Factor VIII Factor IX Hemarthrosis, oropharyngeal or dental,
factor epistaxis, hematuria
Inheritance X-linked X-linked Major bleeding
recessive recessice Target 80-100% q8-12h; 7-14 days
Incidence 1/10.000 1/50.000 (50U/kg)
CNS trauma, hemorrhage, lumbar Type 1: Partial quantitative deficiency
puncture Type 2 Qualitative deficiency
SUrger Type 3 Total quantitative deficiency
Retroperitoneal hemorrhage
GI bleeding Assay 1 2 3
Adjunctive therapy vWF Decrease Normal Decrease
Amicar or DDVAP (for mild disease only) antigen
vWF Decrease Decrease Decrease
Complications of therapy activity
Multimer Normal Normal Absent
Formation ofd inhibitors (antibodies) analyses
10-15% of severe hemophilia A patients
1-2% of severe hemophilia B patients
Treatment of von Willebrand disease
Viral infections Cryoprecipitate
Hepatitis B Source of fibrinogen, factor VIII and
Hepatitis C VWF
HIV Only plasma fraction that consistently
Humarn parvovirus contains VMF miltimers
Hepatitis A
Other DDAVP (deamino08arginine vasopressin)
Increase plasma VWF levels by
Treatment of hemophilia B stimulating secretion from endothelium
Durationof response is variable
Agent Not generally used in type 2 disease
High purity factos IX Dosage 0.3 ug/kg q 12 hr IV
Recombinant human factor IX
Factor VII concentrate (intermediate purity)
Dose Virally inactivated product
Initial dose: 100U/kg
Subsequent: 50U/kg every 24 hours Vitamin K deficiency

Von Willebrand factor Source of vitamin K Green vegetables

Synthesis in endothelium and Synthesized by
megakaryoscytes intestinal flora
Forms larger multimer Required for Factor II, VII, IX, X
Carrier of factor VII synthesis Protein C and S
Anchors platelets to subendothelium Causes of deficiency Malnutrition
Brisdge between platelets Biliary obstruction
In heritance autosomal dominant Malabsorption
Incidence 1/10.000 Antibiotic therapy
Clinical features mucocutaneous bleeding Treatment Vitamin K
Fresh frozen plasma
Laboratory evaluation of von Willebrand

Common clinical conditions associated with Intravascular clot
Disseminated Intravascular Coagulation Decrease platelets and schistocytes
Activation of both coagulation and fibrinolysis
trigerred by Disseminated Intravascular Coagulation
Treatment approaches
Sepsis Obstetrical Treatment of underlying disorder
complications Anticoagulant with heparin
Amniotic fluid Platelet transfusion
embolism Fresh frozen plasma
Abruption placentae Coagutlation inhibitor concentrate
Trauma Vascular disorders (ATIII)
Head injury Reaction to toxin (e.g
Fat embolism snake venom, drugs) Liver Disease and Hemostasis
Malignancy Immunologic disorders 1. Decreased synthesis II, VII, IX, X,XI
Severe allergic reaction fibrinogen
Transplant rejection 2. Dietary Vitamin K deficiency
(Inadequate intake or malabsorption
Disseminated Intravascular Coagulation 3. Dysfribrinogenemia
Systemic activation of 4. Enhacned fibrinolysis (decreased alpha-
2 antiplsmin
5. DIC
6. Thrombocytopenia due to

Management of Hemostatic Defects in Liver

Intravascular deposition Depletion of platelets and Disease
of fibrin coagulation factors
Treatment for prolonged PT/PTT
Vitamin K 10 mg SQ x 3 days 0usually
Fresh frozen plasma infusion
Thrombosis of small and Bleeding 25-30% of plasma volume (1200-1500
midsize vessels with organ ml)
failure Immediate but temporary effect

Treatment for low fibrinogen

Consumption of coagulation factors presence of Cryoprecipitate (1 unit/10kg body
FDPS weight)

aPTT Treatment for DIC (elevated D-dimer, low

PT factor VIII, thrombocytopenia
TT Replacement therapy
Decrease fibrinogen

Presence of plasmin
Vitamin K deficiency due to warfarin overdose Smoking
Managing high INR values Drugs -> Birth Control high estrogen
Congestive Heart failure
Clinical situation Guidelines Central Venous Pressue (CVP) catheter
INR therapeutic-5 Lower or omit next Pacemake/Defibrillator placement
dose; Resume Neurological deficits CVA, MS, Spilnal
therapy when INR is cors
therapeutic Superficial vein thrombosis
Herediatry deficiencies Protein C/S,
INR 5-9; no bleeding Lower or omit next antithrombin III
dose; Resume
therapy when INR is Hypercoagulability: Risk Factors
therapeutic Recent surgery
Omit dose and give o Tissue factor exposure
vitamin K (1-2.5 mg especially orthopedic
po) o Total hip replacement 25% w/o
Rapid reversal; prophylaxis (3-4% fatal)
vitamin K 2-4mg po o Reduced 30-50% with
(repeat) prophylaxis
INR >9; no bleeding Omit dose, give o Traumatic hip fx: 50%
vitamin k 3-5 mg po; o Total knee replacement 60%
repeat as necessary Fractures or other traumas.
Resume therapy at
lower dose when INR Virchows Classic Triad
Three Major Elements that promote thrombosis
Hypercoagulability more deaths from clotting
than bleeding Endothelial injury
Decrease in blood flow
Killer Clots Imbalance between procoagulant and
Myocardial infarction o (Hypercoagulable state)
Deep venous Thrombosis -> Pulmonary
Emboli Endothelial Injury
Cerebral vascular accidents Mechanical trauma
Thrombotic Emboli-sources Artherosclerosis (intrinsic pathway)
o Carotids Endotixins from bacteria
o Heart-Atrial fibrillation, CHF Proteases and cytokines of inflammation
Deep Venous Thrombosis/ Venous Thrombo Hypoxia
Decreased in Blood flow
VTE risk Heart failure (HF) causes stasis
Malignancy Atrial fib/flutter
Trauma Myocardial infarction
Surgery- Extremity Immobilization
o Long travel and long flight o Advanced age (fibrinogen levels
economy class syndrome increase) OCP, pregnancy
o Casting o Surgery, trauma
o Bedridden (stroke Hypercoagulable state from other
Thrombophilia (hypercoagulable) disease
o Malignancy
Genetic: o Renal-nephrotic syndrome
o 5-8% of population has one o thick blood polycythemia,
genetic clotting disorder; 25- Sickle cell
50% will have F. V Leiden
AGE: at onset <50 years Treatment of Venous Thromboembolism
none Low risk and clearly identifiable cause
o Frequently triggered by 2nd risk o 3 months oral anticoagulation
factor Medium risk
FAMILY HISTORY: frequently positive o 6 months oral anticoagulation
PAST HISTORYT: recurrent events High risk
Get in trouble when 2nd factor is o Life long anticoagulant with
present INR 2-3

INHERITED Hypercoagulable Disorders Treatment for Hypercoagulation

Activated Protein C resistance
o Factor V Leiden genetic ANTICOAGULANTS
mutation Heparin, low molecular heparin, warfarin
o 25% in patient with family hx of (Coumadin)
o 5% of white populations Platelet anticoagulants
o #1 cause of inherited Inactivates COX necessary for production of
thrombophilia named for city in Thromboxane A2
Netherlands o Aspirin-irreversibly
Hyper-homocystenemia under debate o NSAIDS: reversible inactivation of
Antithrombin II deficiency platelets
Protein C deficiency (1:100_ ADP INHIBITORS
Protein S deficiency o Ticlopoidine-Tietid
Prothrombin 20210 mutation altered o Clopidogrel-Plavix
thrombin production
Fibrinolytic agents
Acquired Hypercoagulable Disorders o Streptokinase, urokinase, tissue
Antiphospholipid Antibody Syndrome plasminogen activators (1-PA)
Found in some cases of SLE, syphilis,
rheumatoid arthritis Heparin-Low m,olecular weight
LMWH depolymerized (fractioned)
Acquired hypercoagulable state o More reliable, predictable
o Monitoring PTT not required
Physiologic or thrombogenic stimulus o SQ administration; Out patient therapy
o Acture phase (reactants from possible
inflammation o Pregnancy-prophylaxis only 2 & 3
o Lower risk of thrombocytopenia
o Enoxparin (Levenox), Dalterparin

Dabigtran- PRADAXA

Direct Thrombin inhibitor

o No Protime necessary
o Stroke preventions, DVT Treatment
o Bleeding
o Renal adjustment necessary

Indications for thrombolytics Clot busters

o Acute myocardial infarction (AMI)
o Deep vein thrombosis (DVT)
o Pulmonary embolism (PE)
o Acute ischemic stroke (AIS)
o Acute peripheral arterial occlusion
o Occlusion of indwelling catheters

Contraindications to Thrombolytics
History of hemorrhagic stroke <2
CNS neoplasm, AV malformations, or
aneurysm, or CNS surgery <<2 months
Severe uncontrolled hypertension (over
200/130 or complicated by
retinovascular disease or
Ongoing (active) bleeding
s/p recent significant surgery
known bleeding disorder
MI due to aortic dissection
Allergy t o agent planned
Many relative contraindications