4. Coagulation Factor Deficiencies
• Hemophilia A
• Von Willibrand’s Disease
• Hemophilia B
• Factor XI deficiency (Hemophilia C)
• Deficiency of Factor II, V, X
• Factor VII deficiency
• Factor XIII deficiency
5. Hemophilia
• A = factor VIII deficiency
• B = factor IX deficiency
• Sex-linked recessive disorder
• May not bleed immediately after trauma
• Severity:
– <1% : severe: spontaneous bleeding
– 1 – 5% : moderately severe: bleeding severely after
trauma and minor surgery
– 5 – 30% : mild
6. Hemophilia: Treatment
• Genetic counseling
• Factor replacement
– FFP 1 ml contends FVII 1 U, FIX 1 U
– FFP 1 U = 200 ml = FVIII 200 U, FIX 200 U
– Cryoprecipitated 1 U = 80 – 100 ml
– Plasma volume = 40 ml/kg
– FVIII 1 U/BW 1 kg => increases activity 2%
– FIX 1 U/BW 1 kg => increases activity 1%
– However, maximum dose is 10 – 20 ml/kg (increases
activity 30%) due to volume overload
13. Brunicardi FC et al.
Schwartz’s Principles of
Surgery. 10th ed. McGraw-Hill
Education, 2015. page 90
14. Heparin-induced thrombocytopenia (HIT)
• Ab against platelet factor 4 (PF4) formed
during heparin exposure, affect platelet
activation and endothelial function resultant
in thrombocytopenia and intravascular
thrombosis
• Platelets fall 5 – 7 days after starting heparin
• Suspected in patients on heparin with
plt<100,000, or falls 50% from baseline
15. • Stop heparin
• Start alternative anticoagulant
– Lepirudin, argatroban, danaparoid
– Argatroban for patients with renal insufficiency
Heparin-induced thrombocytopenia (HIT):
Treatment
16. TTP and HUS
• Hemolytic Uremic syndrome: MAHA, uremia,
thrombocytopenia
• Thrombotic thrombocytopenic purpura: HUS +
fever + neurologic signs/symptoms
• Both are the result of platelet activation and
formation of platelet thrombi
• Treatment:
– Discontinuation of involved drugs
– FFP
– Plasma exchange
17. Sequestration
• From: portal hypertension, sarcoid, lymphoma,
Gaucher’s disease
• Total body platelet mass is normal but large
amount is in enlarged spleen
• Splenectomy is not indicated to correct
thrombocytopenia caused by portal
hypertension
18. Qualitative Platelet Defects
• Related to platelet function
• May present a normal platelet count
• Etiology:
– Massive transfusion
– Therapeutic platelet inhibitor: ASA, clopidogrel,
prasugrel, dipyridamole, GP Iib/IIIa inhibitors
– Diseases: liver disease and uremia
25. Primary fibrinolysis
• may occur in patients following prostate
resection (releasing urokinase) or
extracorporeal bypass
• Treatment: ɛ-aminocaproic acid and
tranexamic acid
26. Myeloproliferative Diseases
• polycythemia vera
• Increased blood viscosity increased stasis
spontaneous thrombosis
• Spontaneous hemorrhage also noted
• Treatment: reduction of thrombocytosis by low
dose ASA, phlebotomy, hydroxyurea
27. • Effecting both platelet and coagulation
• Result: thrombocytopenia and prolonged PT
• Etiology of thrombocytopenia:
– Hypersplenism
– Reduced production of thrombopoietin (TPO)
– Immune-mediated destruction of platelets
• Treatment for invasive procedure: platelet
transfusion
Coagulopathy of Liver Disease
28. • Role of liver in coagulation system:
– Synthesis of coagulation factors
– Absorption of vitamin K depending on bile
production
• Disturbance in coagulation mechanism
increases both bleeding and thrombotic risk
• Treatment: FFP
Coagulopathy of Liver Disease
29. Coagulopathy of Liver Disease
Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed. McGraw-Hill Education, 2015. page 92
30. Coagulopathy of Trauma
• Vicious cycle
• Mechanisms:
– Dilutional effect
– Shock inducing systemic activation of
anticoagulant and fibrinolytic pathways
• Treatment: FFP transfusion
36. Heparin
• Selective inhibitor of thrombin
• Half life 90 – 120 min
• Use: VTE prophylaxis
• Dose: 80 U/kg IV bolus, then 18 U/kg/hr
titrate 50 -100 U/hr q6hr
• Monitoring: aPTT ratio 1.5 – 2.0 q6hr
• Revered with protamine sulfate (1 – 1.5 mg for
100 U of heparin)
37. LMWH and others
• LMWH = low molecular weight heparin
– :Factor Xa inhibitor
– :enoxaparin, Fondaparinux, Rivaroxaban (oral form),
dabigatran
• Dose: enoxaparin 100mg/ml, 3 ml per vial
– <50 kg: 0.4 ml
– >50 kg: 0.6 ml
– CrCl < 30: OD
– CrCl > 30: q12hr
• No monitor
38. Warfarin
• Standard for long term arterial and venous
thromboembolism prophylaxis
• Vitamin K antagonist: inhibit factor II, VII, IX,
X, protein C and S
• Major complications:
– Bleeding
– Recurrent thrombosis
– Skin necrosis
39.
40. Warfarin: Management
• Starts with warfarin 3 mg/day
• F/U PT next 3 – 5 days
• Therapeutic INR range: 2 - 3
• Adjust dose by 5 – 20% of mg/wk
43. Antiplatelet Agents
• ASA, ticlopidine, clopidogrel, prasugrel,
dipyridamole
• Usage: prevention of cardiovascular events:
MI, stroke, PAD
44.
45. Fibrinolytic Agents
• Plasminogen activator
• examples: urokinase, streptokinase, rtPA
• Applications:
– STEMI and stroke fast track
– Acute limb ischemia and peripheral bypass graft
occlusion
– Controversy in DVT and PE
• Complications: bleeding, rethrombosis
46. Mulholland MW et al. Greenfield’s Surgery
Scientific Principles and Practise. 5th ed.
Philadelphia: LIPPINCOTT WILLIAMS &
WILKINS, 2011. page 86
47. Local Hemostasis
• : the goal is to prevent further blood loss from
a disrupted vessel that has been incised or
transected
• Mechanical procedures
• Thermal agents
• Topical hemostatic agents
48. Mechanical Procedures
• Oldest method: digital direct pressure (at
bleeding site VS proximal)
• Tourniquet, Pringle maneuver
• Packing during laparotomy
• Simple ligature
• Transfixion suture for pulsatile arteries
• Bone wax
51. Thermal Agents (electrocautery)
• Generates heat by alternating current source
transmitted via conduction from instrument to
tissue protein denaturation coagulation
• A negative grounding placed beneath the
patient to avoid skin burns
52. Topical Hemostatic Agents
• The ideal topical hemostatic agent has
significant hemostatic action, minimal tissue
reactivity, nonantigenicity, in vivo
biodegradability, ease of sterilization, low cost,
and can be tailored to specific needs
• Clotting activation
• Just adjunct, not main
• Examples: Gelfoam, Surgicel, Avitene,
Floseal, Vitagel
56. Packed red blood cell (PRC)
• 200 ml
• Shelf life 42 days under 1 – 6oC
• Product of choice
• 1 PRC: increases Hb 1g/dL, Hct 3%
• Leucocyte-poor and leucocyte depleted PRC:
use to prevent febrile nonhemolytic transfusion
reaction
57. Platelets
• Normal: 150,000 – 450,000 / mcL
– <100,000: bleeding after major trauma/surgery
– <50,000: minor trauma
– <10,000 – 20,000: spontaneous bleeding
• Life span 7 – 10 days
• Shelf life 120 hr
• Most common abnormality of hemostasis in
surgical patients
58. Platelets: treatment
• Blood component:
– Platelet concentrates: (PC) 1U = 50 ml = increases
platelet 5,000 – 8,000
– Single donor platelet (SDP) = 200 ml = increases
platelet 20,000
• PC transfusion (U) = 0.1 U/kg x BW
• Cross-matching is not necessary
• Keep platelet when:
– >100,000 : major surgery
– > 50,000 : minor surgery, LP
– >10,000 – 20,000: spontaneous bleeding prevention
59. Fresh Frozen Plasma (FFP)
• 250 ml
• Store of vitamin K-dependent factor (II, VII,
IX, X) and factor V
• Stored up to 5 days after warmed up
• Use: massive transfusion, coagulopathy and
factors deficiency
• Cross-matching is essential
60. Typing and Crossmatching
• Routinely ABO and Rh
• Between donor’s RBC and recipient’s serum
• In Rh –ve patient: Rh +ve blood is acceptable but
not in women in child-bearing age
• In emergency transfusion: O-ve or type-specific
• Timing:
– Full crossmatch: 45min – 1hr
– Type-specific: 5-10min
– O-ve: availiable stat!
61. Autologous Transfusion
• 5 U can be collected for elective surgery
• Patient should have Hb 11 g/dL or Hct 34%
• First unit is in 40 days before operation,
interval 3 – 4 days, and the last can be at 3
days before operation
• Recombinant human erythropoietin (RHuEPO)
accelerates generation of RBC
62. Tranexamic Acid (Tranxamine, TXA)
• Inhibitor of plasminogen activation and
plasmin activity
• thus preventing clot breakdown rather than
promoting new clot formation
• Not affect platelet count
• Application: CAGB, liver transplantation, hip
and knee arthroplasty
• ADR: GI and visual disturbances,
thromboembolic event
63. Indications for Blood Replacement
• Improvement in oxygen-carrying capacity
• Treatment of anemia
• Volume replacement (bleeding > 2L)
64. Anemia: Treatment
• Preoperative Hct: 30%, Hb: 10 g/dL
• In critical illness and chronic anemia: keep Hb
7 – 9 g/dL
• In patients with ischemic heart disease: Hb 7
g/dL
65. Damage Control Resuscitation
• Prevention of lethal triad
• Composed of:
– Permissive hypotension (hypotensive resuscitation,
SBP < 90 mmHg, MAP 65 mmHg)
– minimizing crystalloid-based resuscitation
– immediate release and administration of
predefined blood products
66.
67.
68. Complications of Transfusion
• Hemolytic Reactions
• Nonhemolytic Reactions
• Allergic Reactions
• Respiratory Complications
• Transmission of Diseases
71. Nonhemolytic Reactions
• Febrile
– Fever > 1oC, 1% of transfusion
– Mechanism: cytokines, host Ab
– Prevention: LPRC
• Bacterial contamination
– Fever and sepsis
– Most common: Gram-negative (grow in 4oC)
– Treatment: antibiotics
– Prevention: stored platelet < 4days
72. Allergic Reaction
• 1% of all transfusions
• Common in FFP and platelets
• S/S: usually mild: urticaria, rash, flushing
– Anaphylactic shock is rare but develops
• Caused by transfusion of antigens or
antibodies which the recipient is
hypersensitive
– IgA deficiency
• Treatment: antihistamine
78. Tests of Hemostasis
• Platelet count
• Bleeding time
• VCT and WBCT
• PT and aPTT
• TEG
79. Bleeding Time
• Detecting platelet and vascular dysfunctions
• Most commonly use: Ivy method
– Cuff 40 mmHg and 5 mm stab incision at flexor
surface of forearm
– Normal: 7 min (5 – 15 minutes)
80. VCT and WBCT
• Use with patients with snake bites
• Venous Clotting Time (VCT)
– 3 tubes with blood 1 ml per each after 5 min,
bend 90o of tube q1min until no blood comes
– Normal: < 20 min
• Whole Blood Clotting Time (WBCT)
– 1 tube, 2 ml, waiting for 20 minutes and bend the
tube, if not clot positive
81. Prothrombin Time (PT)
• measures the function of factors I, II, V, VII,
and X.
• Best for detecting vitamin K deficiency and
monitoring warfarin therapy
• Due to variations: International Normalized
Ratio (INR) becomes choice to report PT value
• Normal: INR 1.3 – 1.5
• INR = measure PT / normal PT
82. Activated Partial Thromboplastin Time
(APTT)
• measures function of
– factors I, II, and V of the common pathway
– factors VIII, IX, X, and XII of the intrinsic
pathway
• Suite for monitoring of heparin therapy
• Normal: aPTT ratio 1.5 – 2.5
83. Thromboelastography (TEG)
• Or ROTEM (Rotational Tromboelastometry)
• Whole blood-viscoelastic testing
• dynamically
• measures the interactions of coagulation
factors, inhibitors and cellular components
during the phases of clotting and subsequent
lysis over time
86. How to prepare autologous blood
transfusion?
• First unit is in 40 days before operation,
interval 3 – 4 days, and the last can be at 3
days before operation
• 5 U
• Patient should have Hb 11 g/dL or Hct 34%
• Recombinant human erythropoietin (RHuEPO)
accelerates generation of RBC
87. When should heparin-induced thrombocytopenia
be suspected?
When thrombosis occurs while receiving heparin
or when there is a fall in the platelet count by
greater than 50% or to below 100,000/μl.
88. What are the major endogenous activators of
plasminogen?
Tissue plasminogen activator (tPA) and
urokinase
89. How dose warfarin work as an anticoagulant?
Interfering with vitamin K-dependent factor: II,
VII, IX, X, protein C, protein S
90. How long will ASA affect the platelets?
7 days entire platelet life due to irreversible
effect
91. A 45-year-old woman with deep vein thrombosis
is taking warfarin (Coumadin), 5 mg/d. Seven days after
initiation of therapy, she has warfarin-induced skin necrosis.
Which of the following statements regarding this condition
is true?
(A) It commonly occurs after warfarin therapy.
(B) It usually involves the upper extremities.
(C) It improves with an increase in the dose of Coumadin.
(D) It improves with a decrease in the dose of Coumadin.
(E) It requires cessation of Coumadin and infusion of
heparin.
92. After undergoing a transurethral resection of the
prostate, a 65-year-old man experiences
excessive bleeding attributed to fibrinolysis. It is
appropriate to administer which of the
following?
(A) Heparin
(B) Warfarin (Coumadin)
(C) Volume expanders and cryoprecipitate
(D) Aminocaproic acid (Amicar)
(E) Fresh-frozen plasma and vitamin K
93. References
Brunicardi FC et al. Schwartz’s Principles of Surgery. 10th ed.
McGraw-Hill Education, 2015.
Blecha MJ. General Surgery Absite and Board Review. 4th ed.
McGraw-Hill, 2008.
Cayten CG et al. Lange Q & A Surgery. 5th ed. McGraw-Hill, 2007.
Mattox KL et al. Trauma. 7th ed. McGraw-Hill Medical, 2013.
Mulholland MW et al. Greenfield’s Surgery Scientific Principles and
Practise. 5th ed. Philadelphia: LIPPINCOTT WILLIAMS & WILKINS,
2011.
Semer NB et al. Practical Plastic Surgery for Nonsurgeons.
Philadelphia: Hanley & Belfus, 2001.
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Notas del editor
TXA2, endothelin, serotonin – from endothelial injury cascade, bradykinin and fibrinopeptides – from coagulation schema