DVT Prophylaxis and Pulmonary Embolism Karen Ruffin RN, MSN Ed.
DVT From Pathophysiologi to Prophylaxis 2006
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Transcript of DVT From Pathophysiologi to Prophylaxis 2006
NYOTO WIDYO ASTORO
HEMATOLOGI-ONKOLOGI MEDIK PENYAKIT DALAM RS GATOT SOEBROTO
HEMOSTASIS
Function of HEMOSTASIS
• ARREST BLEEDING• MAINTAIN BLOOD IN FLUID STATE
HEMOSTASIS
• Primary Hemostasis– Blood vessel contraction– Platelet Plug Formation
• Secondary Hemostasis– Activation of Clotting Cascade – Deposition & Stabilization of Fibrin
• Tertiary Hemostasis– Dissolution of Fibrin Clot– Dependent on Plasminogen Activation
HemostasisBV Injury
PlateletPlateletAggregation
Blood VesselBlood Vessel Constriction
CoagulationCoagulation Cascade
Stable Hemostatic Plug
Fibrin formation
Reduced
Blood flow
Tissue Factor
Primary hemostatic plug
Neural
Lab Tests•CBC-Plt•BT,(CT)•PT•PTT
Plt StudyMorphologyFunctionAntibody
Platelet Adhesion
and Activation
The primary haemostatic system:haemostasis and platelet plug formation
Vascularinjury
Formation ofplatelet plug
exposed sub endothelial tissue
trombosit
endothelial cells
sub endothelial tissue
Platelet aggregation
Adhesion
Activation
Aggregation
White clot
Primary haemostasis
The haemostatic system:secondary haemostasis and clot formation
ThrombinProthrombin
FibrinExtrinsic pathway
Intrinsic pathway
Factor Xa
Fibrin threads
Coagulation cascadeleads to clot formation
Clot growth
Fibrinogen
Activation of the coagulation cascade leads to generation of thrombin and, in turn, fibrin
VIIa
Coagulation balance: endogenous activators : the core role of factor Xa
Boneu B, et al. Sang Thrombose Vaisseaux 1998; 10:291–313.
Cellular thromboplastin
Ca2+
Xa
XIa
Intrinsic system Extrinsic system
X
II
IX
XIIIa
XI
XII XIIa
Soluble fibrinFibrinogen Fibrin (clot)
XaVa
PLCa2+
VII
ThrombinIIa
IXaVIIIaCa2+
PL
DIC
Disseminated Intravascular Coagulation
“ ….an acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes. It can originate from and cause damage to the microvasculature, which if sufficiently severe, can produce organ dysfunction…”
Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis, Paris July 2001
DISSEMINATED INTRAVASCULAR COAGULATION
• Activation of coagu-lation by triggering events
• Depends on host response• Influenced by comorbid
conditions• Thrombosis and bleeding
Underlying disorder
Systemic activation of coagulation
Widespread intravascular fibrin deposition
Consumption of platelets and clotting factors
Thrombosis and organ failure
(severe) Bleeding
DIC in the Surgical patient
• Massive trauma / burns• Head injuries• Disseminated malignant disease• Limb gangrene• Infection / sepsis• Hemodynamic problems including hypoxia
Minimal clinical findings in the diagnosis of DIC
• Clinical evidence of thrombosis, hemorrhage, or both, and
• Should be occuring in the appropriate clinical setting
Laboratory criteria based on DIC pathophysiology
Evidence of procoagulant activationEvidence of fibrinolytic activationEvidence of inhibitor consumptionEvidence of end-organ damage or failure
Evidence of procoagulation
• Elevated prothrombin fragment 1+2• Elevated fibrinopeptide A• Elevated fibrinopeptide B• Elevated thrombin-antithrombin
complex• Elevated D-dimer
Evidence of fibrinolytic activation
• Elevated D-dimer• Elevated FDP• Elevated plasmin• Elevated plasmin antiplasmin complex
Evidence for inhibitor consumption
• Decreased AT-III• Decreased alpha-2-antiplasmin• Decreased heparin cofactor II• Decreased protein C or S• Elevated TAT complex• Elevated PAP complex
Evidence for end-organ damage
• Elevated LDH• Elevated creatinine• Decreased pH• Decreased paO2
Needs 2 out of 4 above items for diagnosis
Treatment of DIC
• Cornerstone: management of underlying problem
• Plasma and/or platelet replacement
• Anticoagulant strategies• Administration of coagulation
inhibitors
TROMBOSIS
What is thrombosis ?• Thrombosis is the formation or
presence of a blood clot inside a blood vessel or cavity of the heart
Thrombosis• Arterial thrombosis (white
thrombus)• Venous thrombosis (red
thrombus)
Pathophysiology
Pathophysiology thrombosis
HIGH FLOW : ARTERIAL CIRCULATION
Fibrin PlateletsRBCs
White Thrombus
SLOW FLOW : VENOUS CIRCULATION
Fibrin PlateletsRBCs
Red Thrombus
RED THROMBUS IN LUMEN OF VEIN
Fibrin PlateletsRBCs
White Thrombus
Fibrin PlateletsRBCs
Red Thrombus
High Flow Slow Flow
Platelets: Role in Thrombosis
RBCs, red blood cells.
Pathogenesis of DVT
Venous thromboembolismVenous thromboembolismVirchow's TriadVirchow's Triad
• StasisStasis• Activation of coagulationActivation of coagulation• Vessel damageVessel damage
Interpretation of Virchow’s triad using modern understanding of the physiologic mechanisms of thrombosis
Virchow’s Triad Modern interpretation
Stasis Immobility: of minor importance except that it may indicate underlying disease activityParalysis induces “ microtears” in venous endothelium
Blood coagulability Impaired inhibition of coagulation Deficiencies of AT III, PC, PS Factor V Leiden, prothrombin 20210Effects of inflammatory cytokines Increased monocytes tissue factor Increased plasminogen activator inhibitor
Venous injury Direct trauma Torsion during surgery Hydrodynamic trauma from tourniquet useEffects of inflammatory cytokines Endothelial cell apoptosis Increased endothelial cell tissue factor Decreased thrombomodulin expression
Medical Illness as the risk factors for DVT
1. Stasis predisposes to venous thrombosis
• By preventing activated coagulation factors from being diluted by non activated blood
• By preventing clearence of activated coagulation factor
• By preventing mixing of activated coagulation factors with their inhibition
Venous stasis is produced
• By immobility• By venous obstruction• By venous dilatation • By increased blood viscosity
KONTRAKSI OTOT
KONTRAKSI OTOT
Medical Illness as the risk factors for DVT
Medical Illness as RISK FACTORS for VTE
Age > 40 years (VTE risk increases with advancing age) Intensive care unit (ICU) admission Prior history of VTE (DVT or PE) Obesity Ischemic (nonhemoragic) stroke Heart Failure Chronic lung disease Respiratory failure Pneumonia Infection Malignancy Thrombophilia (hematological disorder that promote thrombosis) Active collagen-vascular disorder Inflammatory disorder (e.g inflammatory bowel disease, etc) Central venous line/catheter Varicose veins Birth control pills Estrogen replacement therapy Nephrotic syndromeThis is partial list of common risk factors. Clinicians are advised to consider other factor orconditions that may predispose to VTE
Incidence Range of VTE Disease in Western Studies (Medical Illness)
DVT Proximal DVT PE Fatal PE
(%) (%) (%) (%)
AMI 24.0 - 2.6-6.1 -
Stroke 55.0 - 1.6 0.6
Acute medical conditions 16.0 4.9 1.0 0.3
Pathogenesis II 2.Hypercoagulable state(1)
• Activation of blood coagulation– Activation of the intrinsic pathway by
contact of F XII with collagen on the exposed subendothelium of damaged vessel (intrinsic pathway)
– Activation of the extrinsic pathway by the release of tissue thromboplastin into blood stream as a result of cell damage
2.Hypercoagulable state(2)
• Activation of blood coagulation– Endothelial cell activation– Activated leukocyte that migrate to area of
vascular damage
Surgical Procedures as the risk factors for DVT
Pathogenesis II :2.Hypercoagulable State (1)
Activation of coagulation :Laparotomy vs laparoscopy
Rahr HB et al. Thromb Hemost 1994; 71:713-18Rahr HB et al. Thromb Res. 1999; 93: 121-7.
Activation of Coagulation (1)
0
0.5
1
1.5
2
2.5
3
3.5
pre-opDay 1North
F1+2
(nM
)
F1+2 , prothrombin fragment 1+2
00.20.40.60.8
11.21.41.61.8
pre-op
24hpost-op
Laparotomy (n=21) Laparoscopy (n=50)
Activation of Coagulation (2)
00.20.40.60.8
11.21.41.61.8
2
pre-opDay 1Day 7
Sol
uble
fibr
in (m
g/l)
0
1
2
3
4
5
6
7
pre-op
24hpost-op
Laparotomy (n=21) Laparoscopy (n=50)
Activation of Coagulation (3)
0
500
1000
1500
2000
2500
pre-opDay 1Day 7
FbD
P (n
g FE
/MI)
050
100150200250300350400450
pre-op
24hpost-op
Laparotomy (n=21) Laparoscopy (n=50)
FbDP, fibrin degradation productsFE, fibrinogen equivalents
Pathogenesis III3.Vascular damage(1)
• Caused shedding of endothelial • Nondenuding• Result in the exposure of blood to
subendothelium
3.Vascular damage (2)
• Activation of the extrinsic pathway due to tissue thromboplastin derived from the vascular damage
• Vascular damage that is accompanied by endothelial cell detachment probably contribute to venous thrombosis in patient undergoing hip surgery, knee surgery
Surgical Procedures as the risk factors for DVT
Classification of DVT risk• Low risk Minor surgery Age <40 No other risk factors• Moderate risk
Major surgery Age >40
No other risk factors• High risk Major surgery Age >40 MI Additional risk factors
• Highest risk Major surgery Age >40 History of VTE Hip fracture THR or TKR CVA Spinal cord injury Trauma Malignancy Congenital
hypercoagulability
Chest 1998;114:531S-60S
VTE, venous thromboembolism; THR, total hip replacement; TKR, total knee replacement; MI, myocardial infarction; CVA, cerebrovascular accident
Incidence Range of VTE Disease
in Western Studies (Surgical)DVT Proximal DVT PE Fatal
PE (%) (%) (%) (%)
THR 45.0-57.0 23.0-36.0 0.7-30 0.1-0.4
TKR 40.0-84.0 9.0-20.0 1.8-7 0.2-0.7
Hip fracture 36.0-60.0 17.0-36.0 4.3-24.0 3.6-12.9
General surgery 6.0-35.5 6.0-8.0 1.3-2.0 0.6-2.0
Major trauma 28.0-68.0 4.0->50.0 - 0.5-2
•Why does a DVT happen?
Venous thrombosis: pathogenesis and clinical consequences (1)
Stasis leads to the development of a thrombus composed of red cells and fibrin
Slow, turbulent blood flow in valve cusps result in areas of local stasis
Prandoni P, et al. Haematologica 1997; 82:423–428.
Venous thrombosis: clot formation in the venous lumen
Slow turbulent flow in the veins induces stasis and promotes coagulation
1.
Fibrin polymerisation stabilises the clot2. Clot growth3.
Venous thrombosis: pathogenesis and clinical consequences (2)
Deep vein thrombosis
Thrombus growth results in proximal progression along the vein
Pulmonary embolismDamage to veins (PTS)
Prandoni P, et al. Haematologica 1997; 82:423–428.
KAKI KIRI BENGKAK
Risk Factor for DVT according to Virchow’s Triad
Venous stasis Vessel Damage Coagulation activation
Age > 60 yrs +
obesity + +
pregnancy + +
Immobilization or paralysis +
Orthopaedic surgery + + +
Trauma of lower limbs + + +
Cardiac insufficiency +
Myocardial infarction (acute phase)
+ +
Stroke + +
Cancer + +
General surgery + + +
Inherited or acquired haemostasis deficiencies
+
Venous insufficiency or varicosis
+ +
Previous history of deep vein thrombosis
+ + +
EPIDEMIOLOGY
Incidence of thrombosis in United States of America
Disease US incidence Total in US /year Definable /100.000 cases reason
• Deep Vein Thrombosis 159/100.000 398.000 80%
• Pulmonary Embolus 139/100.000 347.000 80 %• Fatal Pulmonary Emb. 94/100.000 235.000 80 %• Myocardial Infarction 600/100.000 1.500.000 67 %• Fatal MI 300/100.000 750.000 67 % • Cerebrovascular thromb. 600/100.000 1.500.000 30 %• Fatal Cereb. Trhromb. 396/100.000 990.000 30 % • Total serious thromb. In US 1498/100.000 3.742.000 50 %• Total deaths from above thrmb. 790/100.000 1.990.000 50 %
• Bick RL, Clin Appl Throm Hemos 3, Suppl 1, 1997
1. Gillum RF. Am Heart J. 1987;114(5):1262–12642. Anderson FA Jr, et al. Arch Intern Med.1991;151(5): 933–9383. Silverstein MD, et al. Arch Intern Med. 1998;158(6):585–593
4. NIH Consensus Development. JAMA. 1986 Aug 8;256(6):744–7495. Giuntini C, et al. Chest. 1995 Jan;107(1 Suppl):3–9S
Deep vein thrombosis (DVT) only
Pulmonary embolism (PE) with
or without DVT
Annual incidence (US data)
<69/100,000<145/100,000
Incidence of VTE: The third most common
vascular disease
Complications ofDeep Vein Thrombosis
• Permanent vascular damage to lower limb
• Post thrombotic venous insufficiency
• Postphlebitic syndrome
• Pulmonary embolism (PE)
• Pulmonary hypertension
TROMBUSEMBOLI
VTE: A strong relationship between DVT and PE
Almost 50% of patients with proximal DVT of the leg have asymptomatic PE1
DVT (mainly asymptomatic) is found in around 80% of patients with PE2
1. Pesavento R, et al. Minerva Cardioangiologica. 1997;45:369–3752. Girard P, et al. Chest. 1999;116:903–908
Embolus
Migration
Thrombus
Annual incidence of leg ulcer after a DVT = 1–2%1
Venous ulcer, a highly chronic condition:1 Cases not healed at 4 months: 50%
2 years: 20% 5 years: 8%
Around 60% of patients have two or more recurrences of venous ulcer
Venous ulcer, a very costly disease:Direct medical costs if no healing at 12 weeks
US$10,00021. Kurz X, et al. Int Angiol. 1999;18(2):83–1022. Blair SD, et al. BMJ. 1988;297:1159–1161
Complications of VTE: Leg ulcer, a severe consequence
Post Thrombophlebitic syndrome
Post Thrombophlebitic syndrome
Post Thrombophlebitic syndrome
Post Thrombophlebitic syndrome
Post Thrombophlebitic syndrome
Post Thrombophlebitic syndrome
Economic burden of VTE
1. Bick RL. Clin Appl Thromb Hemost. 1999;5(1):2–9 2. Medicare & DRG. 1996
3. Bergqvist D, et al. Ann Intern Med. 1997;126:454–457
Direct inpatient costs of a VTE event are comparable with myocardial infarction (MI) or stroke1,2
Additional long-term healthcare costs of a DVT: 75% of the initial cost3
Average cost per admission in the US ($)
PE1
DVT1
MI2
Stroke2
12,595
9,337
9,643
6,367
0 5000 100002500 7500 12500
Incidence Range of VTE Disease
in Western StudiesDVT Proximal DVT PE Fatal
PE (%) (%) (%) (%)
THR 45.0-57.0 23.0-36.0 0.7-30 0.1-0.4
TKR 40.0-84.0 9.0-20.0 1.8-7 0.2-0.7
Hip fracture 36.0-60.0 17.0-36.0 4.3-24.0 3.6-12.9
General surgery 6.0-35.5 6.0-8.0 1.3-2.0 0.6-2.0
Major trauma 28.0-68.0 4.0->50.0 - 0.5-2
AMI 24.0 - 2.6-6.1 -
Stroke 55.0 - 1.6 0.6
Acute medical conditions 16.0 4.9 1.0 0.3