Coagulation System (Part II) Flashcards
Must be tested within 24 hours of the time of collection
PT
Must be tested within 4 hours of the time of
collection
APTT
PT reagents (or thromboplastin, tissue thromboplastin) consists of:
tissue factor
phospholipids
calcium chloride.
It is most sensitive to factor VII deficiencies
Prothrombin Time (PT)
Is used most often to monitor the e ects of
therapy with Coumadin
Prothrombin Time (PT)
Prolonged PT results in:
• DIC
• Liver disease
• Vitamin K deficienc
Is employed to monitor the e ects of UFH and to detect LAC and specific coagulation factor antibodies (anti-factor VIII antibody)
Partial Thromboplastin Time (APTT)
Is prolonged in all congenital and acquired procoagulant deficiencies (except VII and XIII)
Partial Thromboplastin Time (APTT)
PTT Negatively charged particulate activator
kaolin, ellagic acid, silica, or celite
PTT Is prolonged when there is a deficiency of one or more of the following coagulation factors:
• II, V, VIII, IX, X, XI, XII
• I (if <100 mg/dL)
Most common deficiencies of PTT
• Factor VIII (Hemophilia A)
• Factor IX (Hemophilia B)
• Factor XI (Rosenthal syndrome)
Distinguish LACs from specific inhibitors and factor deficiencies
PTT Mixing Studies
In PTT Mixing Studies UFH may be neutralized with
polybrene or heparinase
Commercially prepared bovine thrombin reagent cleaves fibrinopeptides A and B from plasma fibrinogen to form a detectable fibrin polymer
Thrombin Clotting Time
Is used to determine whether UFH is present
whenever the PTT is prolonged
Thrombin Clotting Time
May also assess the presence of the oral direct
thrombin inhibitor dabigatran.
+ drug = markedly prolonged
Thrombin Clotting Time
provides quantitative measure of dabigatran
Plasma-diluted TCT
Reptilase is a thrombin-like enzyme isolated from the venom of
Bothrops atrox (lancehead viper)
Venom Activated Assays:
Cleaves fibrinopeptide A only
Reptilase Time
Venom Activated Assays:
Useful for detecting hypofibrinogenemia or
dysfibrinogenemia
Reptilase Time
Russell Viper Venom (RVV) from the
Daboia russelii viper
Venom Activated Assays:
triggers coagulation at the level of factor X
Russell Viper Venom Test
List the Coagulation Factor Assays
- Fibrinogen Assay
- Single-Factor Assays using the PTT
- Nijmegen-Bethesda Assay
- Single-Factor Assays using the PT
- Factor XIII Assay
Clot-based method of Clauss
Fibrinogen Assay
• A modification of TCT
•Is the recommended procedure for estimating fibrinogen function
Fibrinogen Assay
Reagents of Fibrinogen Assay
• Owren bu er
• Bovine thrombin
Explain what happened in Single-Factor Assay using the PTT
● Factor VIII-depleted PPP (alone): ➡️ prolonged PTT
● Factor VIII-depleted PPP + Normal patient plasma: ➡️ PTT reverts to normal
● Factor VIII-depleted PPP + Factor VIII-deficient patient plasma: ➡️prolonged
Confirms and quantifies anti-factor VIII inhibitor (typically IgG4-class immunoglobulin)
Nijmegen-Bethesda Assay
The principles and procedures described in the section on single-factor assay using the PTT system may be applied except that PT reagent replaces the PTT reagent in the test system, and the PT protocol is followed
Single Factor Assays using the PT
is defined as any single or multiple coagulation factor or platelet deficiency
Coagulopathy
Accounts for most instances of fatal hemorrhage
Trauma-Induced Coagulopathy
Resembles the pathophysiology of TTP
Trauma-Induced Coagulopathy
TIC Management
✅ Plasma
✅ FP-24
✅ VWF and Factors V and VIII activities decline to approximately 60% after 5 days of refrigerator storage
the key TIC management component
Plasma
alters the production of the Vitamin K-dependent factors
Liver Disease Coagulopathy: Procoagulant deficiency
In Liver Disease Coagulopathy: Procoagulant deficiency this serves as the sensitive early marker
Factor VII
In Liver Disease Coagulopathy: Procoagulant deficiency this is a more specific marker of liver
disease
Factor V
During Dysfibrinogenemia, the fibrin is coated with excessive
sialic acid
Treatment to Resolve Liver Disease-Related Hemorrhage
- Oral or intravenous vitamin K therapy
- Plasma transfusion
Is often associated with platelet dysfunction and mild to moderate mucocutaneous bleeding (anemia and thrombocytopenia)
Chronic Renal Failure and Hemorrhage
In Chronic Renal Failure and Hemorrhage this coat the platelets
Guanidinosuccinic acid or phenolic compounds
is a state of increased glomerular permeability associated with a variety of conditions
Nephrotic syndrome
In Nephrotic syndrome, what are detected in the urine
factors II, VII, IX, X, XII,
antithrombin,
protein C
Vitamin K Antagonists
Warfarin (Coumadin)
Coumadin overdose:
PIVKA factors
disrupts the vitamin K epoxide reductase and vitamin K quinone reductase reactions
Warfarin (Coumadin)
the single most common reason for hemorrhage-associated emergency department visits
Coumadin overdose
the most common acquired autoantibodies
Autoanti-factor VIII
Factor Inhibitors other than Autoanti-factor VIII
- Antiprothrombin antibodies
- Autoanti-factor XIII
- Autoantibodies to factor V
- Autoanti-factor X
Factor Inhibitors other than Autoanti-factor VIII
Develop as lupus anticoagulant
Antiprothrombin antibodies
Factor Inhibitors other than Autoanti-factor VIII
Documented in patients receiving isoniazid
treatment for tuberculosis
Autoanti-factor XIII
Factor Inhibitors other than Autoanti-factor VIII
May arise spontaneously in autoimmune disorders and after exposure to bovine thrombin in fibrin glue
Autoantibodies to factor V
Factor Inhibitors other than Autoanti-factor VIII
In amyloidosis
Autoanti-factor X
The most prevalent inherited mucocutaneous bleeding disorder
von Willebrand Disease
Leads to decreased platelet adhesion to injure vessel walls
von Willebrand Disease
Describe the 3 domains in vWF
Domain A: supports the receptor site for collagen and GP Ib/IX/V
Domain C: provides a site that binds GP IIb/IIIA Domain D: provides the carrier site for factor VIII
● Caused by autosomal dominant frameshifts, nonsense mutations, or deletions
● Comprises 40-70% of vWD cases
Type 1 von Willebrand Disease
Arises from an autosomal dominant point mutations in A2 and D1 structural domains of the vWF molecule
Subtype 2A
VWF is susceptible to ADAMTS-13
Subtype 2A
Mutations within the A1 domain
Subtype 2B
Raised a nity to GP Ib/IX/V
Subtype 2B
“gain-of-function” mutation
Subtype 2B
A platelet mutation that raises GP Ib a nity for normal HMW-VWF multimers
Platelet-type vWD (PT-VWD) or pseudo-VWD under Subtype 2B
Possesses poor platelet receptor binding despite generating a normal multimeric distribution pattern in electrophoresis
Subtype 2M
Missense mutation in the D9 domain impairs the protein’s factor VIII binding site
Subtype 2N
Factor VIII deficiency despite a normal VWF antigen concentration assay result, normal VWF activity, and a normal multimeric pattern
Subtype 2N
Subtype 2N is also known as
Autosomal Hemophilia
“Null allele” VWF gene translation or deletion mutations
Type 3 von Willebrand Disease
Is the most rare form of VWD
Type 3 von Willebrand Disease
Von Willebrand Disease Treatment
PRICE
(protection, rest, ice, compression, elevation)
Also called Christmas disease
Hemophilia B
Also called Rosenthal syndrome, Factor XI deficiency
Hemophilia C
More than half of the cases have been described in Ashkenazi Jews
Hemophilia C
an e ective form of therapy of Factor V Deficiency
Platelet concentrate
