Hypercoagulable Disorder Demo

Hypercoagulable Disorder Demo

Background of Hypercoagulable Disorders

Category	Features
Classification of venous thromboembolism	*Deep vein thrombosis (DVT)* Typically develops in lower extremity *Pulmonary embolism (PE)* Usually due to DVT propagating to lung
Terminology	*Unprovoked DVT* No identifiable etiology or inciting event *Provoked DVT* Due to a known cause or inciting event *Proximal DVT* Typically in popliteal, femoral, or iliac veins *Distal DVT* Usually below the knee in calf veins Peroneal Posterior Anterior tibial Muscular veins PE located in the main, segmental, or sub segmental branches of pulmonary arteries
Pathogenesis	Altered blood flow (eg, stasis) Altered blood constituents (eg, hypercoagulable state) Vascular endothelial injury

Causes of VTE

Type	Etiologies
Inherited hypercoagulable states	Factor V Leiden mutation Prothrombin gene mutation Protein C deficiency Protein S deficiency Antithrombin deficiency
Acquired risk factors	*Malignancy* Lung Pancreatic Colon Renal cell Prostate *Surgery* Orthopedic Major vascular Neurosurgery Cancer surgery *Drugs* Oral contraceptives Hormone replacement therapy Testosterone Tamoxifen Steroids Trauma Pregnancy Prolonged immobilization Antiphospholipid antibody syndrome Renal disease (eg, chronic kidney disease, nephrotic syndrome) Obesity Heparin induced thrombocytopenia Hyperviscosity (eg, hypergammaglobulinemia, polycythemia) Paroxysmal Nocturnal Hemoglobinuria Inflammatory bowel disease

Clinical Presentation of DVT

Type	Clinical Features
History	*Typical findings* Unilateral leg swelling Pain in extremity Warmth in extremity Erythema in extremity
Physical examination	*Possible findings* Dilated superficial veins Unilateral leg edema with difference in left and right calf diameter Leg pain with tenderness along pathway of involved vein Regional lymphadenopathy

Modified Well’s Scoring System for Diagnosing DVT

Clinical Finding	Score
Active cancer (ongoing treatment within 6 months or palliative)	1
Paralysis, paresis, or recent plaster immobilization of lower extremity	1
Bedridden for > 3 days or major surgery with general/regional anesthesia previous 12 weeks	1
Localized tenderness along distribution of deep venous system	1
Entire leg swollen	1
Calf swelling 3 cm larger than asymptomatic side (measured 10 cm below tibial tuberosity)	1
Pitting edema confined to symptomatic leg	1
Collateral superficial veins (non-varicose)	1
Previous documented DVT	1
Alternative diagnosis at least as likely as DVT (eg, Baker cyst in popliteal region, superficial thrombophlebitis, muscle pull/tear, chronic venous insufficiency)	-2

*Clinical probability score*
DVT likely	>2 points
DVT unlikely	< 2 points

Evaluation of DVT

Type	Clinical Features
Low probability of DVT	*Obtain high or moderate sensitivity D-dimer* Normal D-dimer No further testing needed D-dimer > 500 ng/mL Obtain ultrasound of lower extremity *Ultrasound of lower extremity* Negative No further testing required Positive Start treatment for DVT Nondiagnostic: Consider further testing Repeat ultrasound in 2-3 days CT MRI Venography
Moderate probability of DVT	*Obtain high or moderate sensitivity D-dimer* Normal D-dimer No further testing needed D-dimer > 500 ng/mL Obtain ultrasound of lower extremity *Ultrasound of lower extremity* Negative No further testing required Positive Start treatment for DVT Nondiagnostic: Consider further testing Repeat ultrasound in 2-3 days CT MRI Venography
High probability of DVT	*Ultrasound of lower extremity* Negative No further testing required Positive Start treatment for DVT Nondiagnostic: Consider further testing Repeat ultrasound in 2-3 days CT MRI Venography

Classification of PE

Type	Definitions
Timing	*Acute PE* Symptoms and signs immediately after pulmonary vessel obstruction *Subacute PE* Symptoms and signs days to weeks after initial event *Chronic PE* Symptoms of pulmonary hypertension over many years
Hemodynamic stability	*Massive (high-risk) PE* Hemodynamically unstable with systolic BP < 90 mm Hg *Submassive (low or intermediate risk PE)* Hemodynamically stable PE
Anatomic location	*Saddle* Bifurcation of main pulmonary artery Can extend into right or left main pulmonary artery *Lobar, Segmental, Subsegmental* Distal movement of embolus to lodge in lobar, segmental, or subsegmental branches of a pulmonary artery
Associated symptoms	*Symptomatic* Can have symptoms leading to radiologic confirmation of PE *Asymptomatic* Incidentally found on imaging done for another reason

Clinical Presentation of PE

Type	Clinical Features
History	Dyspnea at rest or with exertion Pleuritic chest pain Cough Orthopnea Wheezing Calf or thigh pain with swelling Hemoptysis
Physical examination	*Vital signs* Tachypnea Tachycardia Possible fever *Extremities examination* Calf or thigh swelling with possible: Erythema Edema Tenderness Palpable cords *Lung examination* Crackles Decreased breath sounds *Cardiac examination* Accentuated P2 component of second heart sound Elevated jugular venous pressure or distention
Laboratory	*Arterial blood gas (ABG)* Unexplained hypoxemia Widened alveolar-arterial gradient Respiratory alkalosis Hypocapnia Possible elevated D-dimer
EKG/ Chest x-ray	*EKG* Usually sinus tachycardia Possible S1Q3T3 *Chest x-ray* Possibly normal Hampton’s hump Shallow, hump-shaped opacity in periphery of lung Westermark’s sign Sharp cut-off of pulmonary vessels with distal hypoperfusion in a segmental distribution within the lung

Modified Well’s Scoring System for Diagnosing PE

Clinical Finding	Score
Clinical signs and symptom of DVT	3
No alternative diagnosis for clinical findings	3
Heart rate > 100 beats/min	1.5
Immobilization > 3 days or surgery in previous 4 weeks	1.5
Previous history of DVT or PE	1
Hemoptysis	1
Malignancy with active treatment in past 6 months or under palliative care	1

*Clinical probability score*
PE likely	>4points
DVT unlikely	<4 points

Evaluation of PE

Type	Clinical Features
Hemodynamically unstable patients	*Stability restored with resuscitation* High suspicion for PE Immediate treatment followed by imaging (CT pulmonary angiogram usually preferred) Low suspicion for PE Obtain imaging for confirming diagnosis (eg, CT pulmonary angiogram) *Unstable despite resuscitation* Obtain bedside ultrasound to evaluate for lower extremity DVT (treat if positive) Can also treat if new right ventricular strain present on EKG
Hemodynamically stable patients	*Use Wells score for estimating probability of PE* Low probability No further testing needed if D-dimer < 500 ng/mL Further testing for elevated D-dimer Intermediate probability No further testing needed if D-dimer < 500 ng/mL Further testing for elevated D-dimer High probability Obtain CT pulmonary angiogram (CTPA) or V/Q scan Treat if imaging positive Use lower extremity ultrasound if unable to do CTPA or V/Q scan Treat if imaging positive Consider pulmonary angiographyif all tests nondiagnostic and high probability

Coagulation Cascade

Treatment of DVT

Type	Recommendations
Proximal DVT	Anticoagulation in all cases unless patient has contraindication
Distal DVT	Anticoagulation somewhat controversial for distal DVT
First DVT	*Initial treatment* Low molecular weight heparin for first 5-7 days *Subsequenttreatment* Either warfarin or direct thrombin inhibitor *Duration of treatment* Treatment for 3-6 months in most patients
Recurrent DVT	Indefinite long-term therapy Consider IVC filter in patients with contraindications for anticoagulation

Treatment of PE

Type	Clinical Features
Hemodynamically unstable patients	*Initial treatment* Resuscitation with IV fluids and vasopressors if needed Oxygen Immediate anticoagulation *Imaging to confirm diagnosis* CTPA once hemodynamically stable Bedside echocardiogram if unable to do CTPA *Treatment* Consider thrombolytics or embolectomy in patients with contraindication to anticoagulation
Hemodynamically stable	*Initial treatment* Oxygen for any hypoxia Consider empiric anticoagulation until confirmation of diagnosis *Imaging to confirm diagnosis* CTPA preferred Bedside echocardiogram if unable to do CTPA
All patents once stable	*Initial treatment* Low molecular weight heparin for 5-7 days Long-term with either warfarin or direct thrombin inhibitor *Duration of therapy for first PE* Treatment for 6-12 months in most patients *Recurrent PE* Indefinite long-term therapy Consider IVC filter in patients with contraindications for anticoagulation

References for Hypercoagulable Disorders

Clinical overview of venous thromboembolism. Schellack, Modau. S Afr Fam Pract 2016;58(1):39-45.
Link to article
Deep venous thrombosis: a literature review.Osman, Ju, Sun, Qi.Int J Clin Exp Med 2018;11(3):1551-1561.
Link to article