THROMBOTIC DISORDERS Flashcards
Is the inappropriate formation of a platelet or fibrin clot that obstructs a blood vessel
Thrombosis
Is a multifaceted disorder resulting from circulatory stasis and abnormalities in the coagulation system, coagulation control mechanisms, platelet function, the blood vessel wall, or leukocyte activation molecules
Thrombosis
Causes ischemia and necrosis
Thrombosis
Also known as hypercoagulability
Thrombophilia
Is the predisposition to thrombosis secondary
to a congenital or acquired condition
Thrombophilia
Known causes of Thrombophilia
• Physical, chemical, or biological events.
• Uncontrolled platelet activation and blood coagulation system activation.
• Blood coagulation control protein deficiencies. • Uncontrolled suppression of fibrinolysis
Confer a risk of venous/arterial thrombosis (a condition called
antiphospholipid syndrome or APS
A cardinal sign of APML is DIC secondary to the release of procoagulant granule contents from malignant promyelocytes
Myeloproliferative neoplasms
Caused by stem cell mutation that modifies membrane-anchored platelet activation suppressors
PNH
most common inherited thrombosis risk factor
FVL gene mutation
second most common inherited thrombophilia in patients with a personal and family history of deep vein thrombosis
Prothrombin G20210A gene mutation
Thrombosis is often associated with a combination of genetic defect, disease, and lifestyle influences
Thrombosis Double Hit
Laboratory Evaluation of Thrombophilia
1.
Antiphospholipid antibodies (LAC, ACL, and Anti-B2-GPI)
Activated protein C resistance and Factor V 2.
Leiden mutation Prothrombin G20210A 3.
4. Antithrombin
5. Protein C control pathway
Comprise a family of immunoglobulins that bind protein-phospholipid complexes
Antiphospholipid Antibodies
APLAs arise as what immunoglobulin
IgG or IgG
Antiphospholipid Antibodies are sometimes called
Nonspecific inhibitors
the plasma protein most often bound
to APLAs
B2-GPI
Most APLAs arise in response to a bacterial, viral, fungal, or parasitic infection or to treatment with one of a variety of drugs
Transient alloimmune APLAs
autoantibodies that arise in collagen vascular diseases, SLE, RA, scleroderma, and Sjogren’s syndrome
Aitoimmune APLA
sign of occult adenocarcinoma such as cancer of the pancreas or colon.
Migratory thrombophlebitis, or Trousseau syndrome
creates protein imbalances that lead to thrombosis through loss of plasma proteins such as antithrom- bin.
Nephrotic Syndrome
throm- botic event occurs in young adults; occurs in unusual sites such as the mesenteric, renal, or axillary veins; is recurrent; or occurs in a patient with a family history of thrombosis (Table 39.3). Because thrombosis is multifactorial, however, even patients with congenital thrombophilia are most likely to experience thrombotic events because of a combination of constitutional and acquired conditions.
Congenital Thrombosis Risk Factors
inadequate dietary folate, vitamin B6, or vitamin B12 levels and with polymorphisms affected the function of methylene tetrahydrofolate reductase (MTHFR) in the methionine metabolic pathway.
antithrombin
may exist in the absence of the FVL mutation and is occasionally acquired in pregnancy or in association with oral contraceptive therapy
APC Resistance
most common inherited thrombosis risk factor,
FVL gene mutation
mutation is the second most common inherited thrombophilia in patients with a personal and family history of deep vein thrombosis.
prothrombin G20210A
associated with a combination of genetic defect, disease, and lifestyle influences.
Thrombosis Double Hit
Antiphospholipid antibodies
comprise a family of immuno- globulins that bind protein-phospholipid complexes.
detected by clot-based profiles;
APLAs include LACs
detected by immunoassay
ACL and anti-!2-GPI antibodies,
nonspecific inhibitors
Because they may bind a variety of protein-phospholipid complexes, they are sometimes
Clot-based screen employs PTT with factor V-depleted plasma.
APC RESISTANCE
Measured by molecular assay
Factor V Leiden mutation* Prothrombin G20210A*
Two clot based assays for LAC profile
DRVVT
PTT
Immunoassay for immunoglobulins of APL family. ACL depends on B2-GPI in reaction mix.
ACL antibody
Immunoassay for an immunoglobulin of APL family. B2-GPI is key phospholipid-binding protein in family.
Anti-B2-GPI antibody*
Digests VIIIa and Va. When consistently below reference limit, follow up with PC antigen assay.
PC ACTIVITY
Serine protease inhibitor suppresses IIa (thrombin), IXa, Xa, XIa. When consistently below reference limit, follow up with AT antigen assay.
AT activity
Digests VIIIa and Va. When consistently below reference limit, follow up with PC antigen assay.
PC activity
PC cofactor. When consistently below reference limit, follow up with total and free PS antigen assay, C4b-binding protein assay.
PS activity
includes a means for detecting unfraction- ated heparin (UFH),
MIXING STUDY
heparinase
Neutralize heparin, although this may be unnecessary because many LAC detection reagents provide heparin-neutralizing poly- brene.
In performing mixing studies, the laboratory professional employs only
PPP
considered the more specific of the LAC assays
DRVVT
Confirms LAC by mixing an aliquot of the patient specimen with the
RVVT high-phospholipid confirmatory reagent,
If the primary reagent result is prolonged over the DRVVT confirm reagent result by a prede- termined ratio or more, typically 1.2, LAC is confirmed.
immunoassay that is not affected by anticoagulant therapy, current thrombosis, or factor deficiencies.
ACL TEST (anti)
in performing mixing studies, the laboratory professional employ
PPP
to detect APL antibodies specific for phosphatidylserine or prothrombin.
antiphosphatidylserine and anti- prothrombin immunoassays
mutation in the factor V
substitutes glutamine for arginine at position 506 of the factor V molecule (FV R506Q)
factor V R506Q mutation is named for the city
The Netherlands in which Bertina first described it, Leiden
factor V Leiden [FVL] mutation,
APC RESISTANCE
chromogenic substrate test
detects quantitative and qualitative AT deficiencies and detects mutations affecting the proteolytic site but not the heparin binding site.
turbidometric micropar- ticle immunoassay
turbidometric micropar- ticle immunoassay
uses a suspension of latex microbeads coated with antibody to antithrombin
Turbidometric micropar- ticle immunoassay
AT concentration is directly proportional to the rate of light absorption change. I LOVE JHOPE
detect both quantitative and qualitative PC deficiencies.
Clot-based or chromogenic functional assays
protein c assay venom
Agkistrodon contortrix
The interval to clot formation is proportional to PS activity ( i love jhope
APC resistance, LAC, and the presence of the therapeutic direct thrombin in- hibitors
argatroban or dabigatran
lipoprotein can be measured by
EIA
Naturally occurring sulfur-containing amino acid intermediate in the metabolism of dietary methionine.
HOMOCYSTEINE
Which comprises DVT and PE, is the third most common thrombotic disease,
Venous Thromboembolic Disease
Often the sufferer first misidentifies DVT as
muscle strain or charles horse
reference method for Pulmonary Embolism
multislice” or spiral chest computed tomography (CT) angiography
generalized and uncontrolled hemostasis activation secondary to a systemic disorder.
DIC
BLACK DEATH
DIC
is the consequence of an immune response to UFH (standard intravenous heparin) and LMWH that is reflected in a reduced platelet count
heparin-induced thrombocytopenia
heparin induced thrombocytopenia antibodies are specific for
platelet factor 4 complexed woth heparin
hapten that triggers immune production of IgG isotype anti-H:PF4 anti- bodies that now bind the H:PF4, targeting a neoepitope on PF4 that is expressed with heparin binding.
H:PF4
pF4 is a positively charged tetrameric protein stored in
alpha granules
