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LUPUS

ANTICOAGULANT

GROUP 1 BSMT 3D
PANIZA, ERIKA JOY M.
VILLANUEVA, ANDREW ARNOLD D.
YANDAN, CHARIS M.
Lupus Anticoagulant
• LA, LAC, Lupus antibody, Lupus inhibitor
• Misnomer->Prothrombotic and Anticoagulant
• aPL
• In Vivo: Procoagulant In Vitro: Anticoagulant
Antiphospholipids
• aPL
• Binding ability with membrane proteins
• Comprises of:
-LA
-Anticardiolipin(ACL)
-Beta 2 Glycoprotein I(B-2GPI)
Etiology
• Antigen-driven immune response
• Autoimmunity
• Unknown inciting antigen and genetic cause
• Occurs in disease states
Epidemiology
• Misnomer
• 1-2% of the population(aPL)
• 30-40% of SLE patients
Pathophysiology
• Phospholipids:
-cell membrane lipids
-ampiphilic (lipid bilayer)
-two fatty acid tails and a phosphate head
In Vivo:
• Human Monocyte Procoagulant Activity(Schved et. al)
• LA enhances monocyte induced TNF-a activity
• TNF-a->upregulation of tissue factor->DIC
• Role of Platelets (Sletnes):
- tenase and prothrombinase complex
-anionic phospholipids and microvesicles shedding
In Vitro:
• Phospholipid dependency of coagulation(Celli et. al)
• LA interferes with PDC pathway->prolongs coagulation
• LA binds to exposed phospholipid layer

• Roubey et. al:


• LA enhances B-2GPI’s anticoagulant property

• Antiphospholipid Syndrome
Laboratory Diagnosis and Findings
1. Complete Blood Count
2. Bleeding Time
3. Clotting Time
4. Activated Partial Thromboplastin Test
5. Prothrombin time
6. Thrombin/Reptilase Time Test
7. Fibrinogen Test
8. Russell Viper Venom Time
9. Factor VIII levels
Laboratory Test Results of Patients with Lupus Anticoagulant
TESTS RESULTS

Complete Blood Count Mild to moderate


THROMBOCYTOPENIA
Bleeding Time PROLONGED/ABNORMAL
Clotting Time PROLONGED/ABNORMAL
Coagulation Tests
Activated Partial Thromboplastin Test PROLONGED/ABNORMAL

Fibrinogen Test NORMAL


Prothrombin time NORMAL
Russell Viper Venom Time ABNORMALLY PROLONGED
Factor VIII levels NORMAL
Confirmatory Tests
ELISA (Enzyme-linked immunosorbent assay)
Radio-immune assay (RIA)
Anticadiolipin anibody tests
Antibodies to beta-2-glypoprotein I (Beta2-GPI)
Complete Blood Count
• Mild to moderate thrombocytopenia (low
platelet count)
Coagulation Factor Assays
• Rules out factor deficiencies
• A panel of factor assays may also help in
detecting lupus anticoagulant.
Activated Partial Thromboplastin Time

• Measures the time required to generate


thrombin and fibrin polymers via the intrinsic
and common pathways
• Patients with Lupus Anticoagulant has a
normal aPTT levels (not prolonged)
Prothrombin Time
• Generation of thrombin and the formation of
fibrin via the extrinsic and common pathway
• Normal in patients with LA
Fibrinogen Test
• This test is also known as a Factor I assay
• Determines the level of fibrinogen in the
blood.
• Normal
Dilute Russell’s viper venom test (DRVVT)

• Russell’s viper venom (RVV) activates factor X


leading to fibrin clot.
• Lupus anticoagulant prolongs clotting time by
binding to RVV and preventing the action of
RVV.
SIGNS AND SYMPTOMS
•Deep Vein Thrombosis
SIGNS AND SYMPTOMS
•Repeated miscarriages or stillbirths
SIGNS AND SYMPTOMS
•Stroke
SIGNS AND SYMPTOMS
•Transitory Ischemic Attack
SIGNS AND SYMPTOMS
•Rash
Less common signs and symptoms
include:
•Neurological symptoms
Less common signs and symptoms
include:
•Cardiovascular disease
Less common signs and symptoms
include:
•Bleeding
TREATMENT
Directed at stopping clot and thrombus formation.

The condition is treated by administering a


combination of blood thinning drugs:

•Shot of heparin combined with


Coumadin.
•Warfarin
•Aspirin
For pregnant women, the pharmacologic
treatment comprises of:

•Low molecular weight heparin and aspirin


in low dose as a replacement for warfarin

If woman experiences repeated miscarriage,


Lovenox and Fragmin are recommended to
be taken after missing a menstrual cycle.
References:
• Nayak, R., Rai, S., & Gupta, A., Essentials in Hematology and Clinical Pathology, JAYPEE BROTHERS MEDICAL
PUBLISHERS (P) LTD, New Delhi, Panama City, London, First Edition, 2012, page 329-331
• Rodak's Hematology Clinical Principles and Applications by Keohone, E.M., et al ( 5th Edition 2016), Page 697-699
• Clinical Hematology Theory and Procedures by M.L. Turgeon 5 th edition pg 452-453
• Origin and pathogenesis of antiphospholipid antibodies by C.M. Celli and A.E. Gharavi
• Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I.
by R A Roubey
• Procoagulant activity of endotoxin or tumor necrosis factor activated monocytes is enhanced by IgG from patients
with lupus anticoagulant by Dr. Jean-Fraņois Schved,
• Endothelial cells stimulated with tumor necrosis factor-alpha express varying amounts of tissue factor resulting in
inhomogenous fibrin deposition in a native blood flow system. Effects of thrombin inhibitors. By D Kirchhofer
• Anionic phospholipids and protein translocation by Bende Kruijff
• https://medlineplus.gov/ency/article/000547.htm
• https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/63678
• https://labtestsonline.org/tests/lupus-anticoagulant-testing
• https://www.mayoclinic.org/diseases-conditions/antiphospholipid-syndrome/symptoms-causes/syc-20355831
• http://syndrome.org/lupus-anticoagulant-syndrome/