LECTURE 2
SECONDARY HEMOSTASIS
Jahan Abdi | Clinical Science | Summer/Fall 2023
OVERVIEW
• Coagulation proteins: synthesis, characteristics, clinical
significance
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Coagulation cascade: proposed models
Regulation of coagulation cascade
Fibrinolysis: components and regulation
Coagulation disorders
Lab diagnosis and clinical correlation
Case studies
COAGULATION FACTORS: TERMINOLOGY/NOMENCLATURE
• 8 factors (“F” for factor) are zymogens (circulating in
plasma in an inactive form)
• FII (prothrombin)
• FVII (stable factor or proconvertin)
• FIX (plasma thromboplastin component, Christmas factor)
• FX (Stuart-Prower factor)
• FXI (plasma thromboplastin antecedent)
• FXII (Hageman factor)
• FXIII (plasma transglutaminase, fibrin-stabilizing factor)
• Prekalikrein ()
• All are serine proteases except FXIII
COAGULATION FACTORS: TERMINOLOGY/NOMENCLATURE
• 7 proteins are co-factors (stabilize and accelerate
proteolytic reactions)
• High molecular weight kininogen (HMWK, Fitzgerald) (co-factor
for FXIIa and PK)
• Tissue factor (FIII, tissue thromboplastin) (co-factor for FVIIa)
• FV (labile factor, proaccelerin) (co-factor for FXa)
• FVIII (labile factor, AHF A) (co-factor for FIXa)
• Protein S (co-factor for activated protein C)
• Thrombomodulin (co-factor for thrombin in protein C activation)
• Protein Z (co-factor for protein Z-dependent protease inhibitor,
ZPI)
COAGULATION FACTORS: TERMINOLOGY/NOMENCLATURE/CLASSIFICATION
• Regulatory proteins (inhibitors)
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•
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Anti-thrombin
Protein C
Heparin co-factor II
TFPI (tissue factor pathway inhibitor)
Other coag factors: FI (fibrinogen), vWF, Ca+ (FIV), phospholipids (PF3)
•
• Suffix “a” after the factor indicates “active or activated”: e.g., VIIa, XIIa
• Roman numerals are based on order of discovery or description of
factors
• We usually call factor I fibrinogen and factor II prothrombin
• PK and HMWK never received a Roman numeral
• Almost all coag factors are synthesized by liver except vWF which is
made by ECs (stored in Weibel-Palade granules) or MKs (stored in PLT
alpha granules)
FUNCTION OF COAGULATION PROTEINS
• Almost all coag factors are synthesized by liver except vWF
which is made by ECs (stored in Weibel-Palade granules) and
MKs (stored in PLT alpha granules)
• vWF: heaviest cog factor (500 - 20000 kd)
• VII: shortest half-life (3-6h), and HMWK the longest
• VIII: is carried in plasma as bound to vWF to maintain 12 h halflife
• Ionized calcium is crucial for coagulation complexes to bind to
platelet or cell membrane phospholipids:
FUNCTION OF COAGULATION PROTEINS
• Coagulation proteins act on
each other in a cascade
reaction
• Each factor (serine protease)
activates the next, and this
continues…
• The outcome is conversion of
fibrinogen (ultimate
substrate) into stable fibrin
clot
FUNCTION OF COAGULATION PROTEINS
• Vitamin K-dependent coag proteins
• SCZ27910 (aka called prothrombin
group)
• They require vit K to become γcarboxylated (hence functional)
• All have 10-12 glutamic acid
residues at N terminal
• Prothrombin group are important for
assembly of coagulation complexes
to generate thrombin
COAGULATION COMPLEXES
• Complex 1: extrinsic tenase
• Tissue factor+VIIa +Ca2++
phospholipid
• Activates X to Xa, and IX to IXa
• Complex 2: intrinsic tenase
• IXa+VIIIa+phospholipid (PLT
surface)+Ca2+
• Activates X to Xa
• Complex 3: prothrombinase
• Xa+Va+phospholipid+Ca2+
• Activates prothrombin to
thrombin
FACTOR VIII AND VON WILLEBRAND FACTOR
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FVIII and vWF are the KEY factors in coagulation (severe bleeding in hemophilia A and
vWD)
FVIII and FIX are encoded by genes on X chromosome
FVIII is degraded in stored plasma faster than other factors
FVIII bounds to and carried by vWF in plasma
vWF is multimeric, subunits of 240kd polymerized to 500-2000kd in MK and Ecs,
degraded to smaller mulitmers by ADAMTS13 (a disintegrin and metalloprotease with a
thrombospondin type 1 motif, member 13), in blood vessels with higher shear rate
vWF has receptors for PLTs and collagen
(bridges PLTs to subendothelium during PLT
adhesion)
vWF level is associated with ABO groups, O
group has lower level
vWF and FVIII are acute phase reactants (APR)
FACTOR XI AND THE CONTACT SYSTEM
• FXII, PK, HMWK constitute the contact system (contact factors,
contact factor complex)
• Contact system is the basis of the aPTT test
• FXII is activated by negatively charged surfaces, FXIIa converts
PK (bound to HMWK) to K, K further activates FXII
• Contact factor complex (HMWK+PK+FXIIa) activates FXI (in turn
activates FIX)
• The most important activator of FXI is thrombin generated by the
extrinsic tenase
• Deficiencies of the contact system factors do not cause bleeding
BUT do prolong aPTT
THROMBIN, FIBRINOGEN, FIBRIN CLOT, FXIII
• Thrombin
• Key serine protease in coagulation with multiple functions
• Major function: cleaving fibrinopeptides A and B (FPA and FPB)
from fibrinogen, triggering spontaneous polymerization, clot
initiation
• Thrombin activates FV, FVIII and FXI (positive feedback)
• Thrombin bound to ………….. activates protein C
• Thrombin triggers ……….. of PLTs
• Thrombin activates TAFI (thrombin activatable fibrinolysis
inhibitor)
• Thrombin activates FXIII to stabilize the fibrin clot
THROMBIN, FIBRINOGEN, FIBRIN CLOT, FXIII
• Fibrinogen
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Primary substrate of thrombin
RI in plasma 200-400mg/dL, an APR
Essential for PLT………. through binding the ………. receptor
PLTs absorb it and store in α granules
• FXIII
• Aka plasma transglutaminase
• Deficiency does not affect PT or PTT
but leads to clinical bleeding
COAGULATION PATHWAYS: IN VITRO MODEL
• Extrinsic pathway
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TF:FVII primary initiator of in vivo coagulation
Reaction order: VII, X, V, prothrombin, and
fibrinogen
Is assessed by prothrombin time (PT) test
• Intrinsic pathway
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Reaction order: XII, pre-K, HMWK, XI, IX, VIII, X,
V, prothrombin, and fibrinogen
Is assessed by activated partial thromboplastin
time (aPTT) test
• Common pathway
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Includes X, V, prothrombin, and fibrinogen
Both tests plus thrombin time (TT)
COAGULATION PATHWAYS: IN VIVO MODEL
• Initiation:
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In vivo, extrinsic tenase complex is the
main initiator of thrombin generation
1-2% FVIIa circulates but inert (requires
TF)
FVII:TF complex activates low level of FX
and FIX, and small amount of thrombin
(ignites more thrombin generation through
positive feedback, max 3%)
• Propagation:
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>95% thrombin is generated
Reactions are on PLT membrane
Large PLT aggregates, intrinsic tenase
activates FX 50-100 fold higher,
prothrombinase complex generates burst of
thrombin
What is (are) missing in this model?
REGULATION OF COAGULATION
Name
Tissue factor pathway
inhibitor (TFPI)
Thrombomodulin
Protein C
Protein S
Antithrombin
Heparin cofactor II
Protein Z-dependent
protease inhibitor
Function
With Xa,
binds TF:VIIa
EC surface
receptor for
thrombin
Serine
protease
Cofactor
Serpin
Serpin
Serpin
Serpin: serine protease inhibitor
FIBRINOLYSIS
• Final stage of hemostatic activation
(hours after)
• Fibrinolytic proteins bind to fibrin as it is
forming
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Main substrate is plasminogen produced by
the liver
ECs secrete TPA (tissue plasminogen
activator) and UPA (urokinase plasminogen
activator), TPA is more effective
TPA degrades fibrin-bound plasminogen to
generate plasmin
Plasmin degrades fibrin (and fibrinogen) into
several fragments (X, Y, D, E, and D-D)
D-D (D dimer) is fibrin-derived and a
diagnostic test for thrombosis and fibrinolysis
CONTROL OF FIBRINOLYSIS
• Plasminogen activator inhibitor-1 (PAI-1) is the main
inhibitor, binds to and inactivates TPA and UPA, it’s a
serpin, produced mostly by ECs and MKs
• α2-antiplasmin (α2-AP) produced by the liver, binds to
and inactivates free plasmin (not plasmin bound to
fibrin)
• Thrombin activatable fibrinolysis inhibitor (TAFI)
synthesized by the liver, activated by the thrombinthrombomodulin complex, blocks binding of TPA and
plasminogen to fibrin and formation of plasmin
BLEEDING DISORDERS AND LAB DIAGNOSIS
Acquired
• Trauma-induced: systemic shock leading to acute reduction in
ADAMTS13, coag factor activation, TF release, and
hyperfibrinolysis.
• Liver disease:
• Reduction in plasma level of SCZ27910
• At the beginning, FVII reduced (shortest half-life), PT is
very sensitive to low FVII, so first PT is prolonged in mild
liver disease, sensitive early maker
• Vit K deficiency has the same effect on PT, FV level
differentiates liver dx from vit K deficiency
BLEEDING DISORDERS AND LAB DIAGNOSIS
• Liver disease:
• Thrombocytopenia due to high sequestration by enlarged
spleen, abnormal PLT function (low aggregation in
aggregometry)
• DIC associated with liver dx due to low production of antithrombin or protein C and S, may be chronic compensated,
or acute uncompensated
• Acute DIC: prolonged PT, PTT, TT, low fibrinogen,
increased D-dimer test
• Chronic compensated DIC: only D-dimer is increased
HEMOSTASIS LABORATORY TESTS IN LIVER DISEASE
Assay
Fibrinogen (FG)
Thrombin time (TT)
Reptilase time
Prothrombin time (PT)
Partial thromboplastin time (PTT)
Factor V assay
Platelet count
Platelet aggregometry
Quantitative D-dimer
Interpretation
>400 mg/dL (elevated) in early, mild liver disease; <200 mg/dL in
moderate to severe liver disease, which causes dysfibrinogenemia
and hypofibrinogenemia
Prolonged in dysfibrinogenemia, hypofibrinogenemia, elevated
fibrin degradation products, and unfractionated heparin therapy
Prolonged in hypofibrinogenemia, significantly prolonged in
dysfibrinogenemia; unaffected by heparin; assay rarely used
Prolonged, even in mild liver disease, because of des-γ-carboxyl
factors replacing normal factors II (prothrombin), VII, and X
Mildly prolonged in severe liver disease because of disseminated
intravascular coagulation (DIC) or des-γ-carboxyl factors II
(prothrombin), IX, and X
Factor V is reduced in liver disease but is unaffected by vitamin K
deficiency, so the factor V level helps distinguish liver disease from
vitamin K deficiency
Mild thrombocytopenia, platelet count <150,000/μL
Mild suppression of platelet aggregation and secretion in response
to most agonists
>240 ng/mL or >500 ng/mL fibrinogen equivalent units (FEUs)
Reptilase time can sometimes be
done instead of TT
BLEEDING DISORDERS AND LAB DIAGNOSIS
Acquired
• Autoanti-factor VIII inhibitor and acquired hemophilia:
• Some patients (older than 65) may develop an
autoantibody against FVII which causes an “acquired
hemophilia” condition (sudden bleeding into soft tissue
or GI bleeding, …)
• May develop in RA, IBD, SLE, or lymphoproliferative
disease (e.g., CLL)
• Could be fatal in 20% cases even if treated
BLEEDING DISORDERS AND LAB DIAGNOSIS
Laboratory investigation of FVIII inhibitors
• PT, PTT, TT, for any patient experiencing sudden anatomic
hemorrhage that mimics acquired hemophilia
• PTT is prolonged but PT and TT are normal
• FVIII level <40units/dL should be established by factor assay
• Mixing studies to confirm presence of the inhibitor:
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Patient’s plasma is mixed 1:1 with normal plasma (NP), prolonged PTT will be
corrected initially but prolonged again after incubation in 370C, why??
If prolonged PTT remains prolonged even after 2h incubation, it indicates
presence of lupus anticoagulants or patient is under heparin therapy
15% of inhibitors (called high avidity) immediately prolong the PTT’s mixture
BLEEDING DISORDERS AND LAB DIAGNOSIS
Congenital
• vWD:
• Autosomal dominant, affecting both sexes, females>males,
qualitative or quantitative changes in vWF due to gene
mutations
• Most common inherited mucocutaneous bleeding disorder
causing decreased PLT adhesion and impaired primary
hemostasis
• Severe quantitative vWF deficiency causes FVIII deficiency
• In “low vWF” cases, vWF plasma level (30-50%) maintain
sufficient FVIII
BLEEDING DISORDERS AND LAB DIAGNOSIS
Congenital
• vWD types and subtypes:
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Type 1: quantitative, 40-70% cases, mild to moderate
Type 2: qualitative types
Type 2A
Type 2B
Type 2M
Type 2N
Type 3: null phenotype, severe vWF deficiency, very low FVIII
VWD LABORATORY DIAGNOSIS
• Very helpful: history of mucocutaneous bleeding and
decreased vWF concentration or activity (function)
• CBC: to rule out thrombocytopenia
• PT and PTT: to rule out factor deficiency other than vWF
• Standard vWD test panel:
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vWF: Rco
vWF: Ag
VWF activity to VWF:Ag ratio
RIPA
FVIII activity
vWF multimers
VWD LABORATORY DIAGNOSIS
Laboratory
Test
VWF:RCo
Type 1
Subtype 2A
Subtype 2B
Subtype
2M
Low
Subtype 2N
Type 3
Low
Low
Low
Normal
Normal to
slightly
decreased
Decreased
Normal
Normal
Very low or
absent
Very low or
absent
VWF:Ag
Low
Platelet
count
PTT
Normal
Normal to
slightly
decreased
Normal
Decreased Normal
Normal
Normal to
slightly
prolonged
Decreased
Slightly low
Normal
Normal
Increased
Normal
Normal to
slightly
prolonged
Normal
Low
Prolonged
Decreased
Normal
Normal to
slightly
prolonged
Decreased
Normal
Normal
pattern
Large and
intermediate
forms absent
Large forms
absent
Normal
pattern
Normal
pattern
All forms
absent
(vWF activity)
RIPA
Factor VIII
activity
VWF
multimers
Absent
<10 units/dL
HEMOPHILIA A, B
• Congenital, single-factor deficiencies
• Marked by anatomic soft tissue bleeding
• X-linked recessive (♂ have the disease, ♀are typically
carriers)
• Hemophilia A: FVIII deficiency (85% of patients)
• Hemophilia B: FIX deficiency (14% of patients)
• Hemophilia C: FXI deficiency (1% of patients)
HEMOPHILIA A
• FVIII protein translated from X chromosome
•
Various deletions, stop codons, nonsense and/or missense
mutations result in quantitative deficiency of FVIII
• FVIII deficiency significantly slows coagulation
pathway production of Thrombin
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Leads to bleeding
• Clinical manifestations include:
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Anatomic bleeds
Deep muscle and joint hemorrhages
Hematomas
Wound oozing after trauma or surgery
Bleeding into the central nervous system, peritoneum,
gastrointestinal tract, and kidneys
Results of Clot-Based Assays in Congenital Single-Factor Deficiencies
Deficient Factor
Fibrinogen
Prothrombin
V
VII
VIII
IX
X
XI
XIII
PT
Prolonged
Prolonged
Prolonged
Prolonged
Normal
Normal
Prolonged
Normal
Normal
PTT
Prolonged
Prolonged
Prolonged
Normal
Prolonged
Prolonged
Prolonged
Prolonged
Normal
TT
Prolonged
Normal
Normal
Normal
Normal
Normal
Normal
Normal
Normal
Reflex Test
Fibrinogen assay
Prothrombin, V, VII, and X assays
Prothrombin, V, VII, and X assays
VII assay
VIII, IX, and XI assays
VIII, IX, and XI assays
Prothrombin, V, VII, and X assays
VIII, IX, and XI assays
XIII quantitative assay
What reflex tests do you suggest for a patient with normal PLT count and
function, normal PT, PTT, TT tests, but with a bleeding history?
LABORATORY INVESTIGATION OF BLEEDING
Correction/Mixing Studies
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Mixing studies are performed on plasma used to distinguish factor
deficiencies from factor inhibitors
Therefore, to differentiate between:
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Factor deficiencies (single or multiple) OR
Specific Factor Antibodies or Inhibitors OR
Non-specific Antibodies or Inhibitors
Normal PT or APTT results require 50% of normal level of factors in
circulation
• Mixing studies help to determine the appropriate next steps to
take in order to diagnose the cause of abnormal APTT and/or PT
results
PT and APTT 50:50 Mixing Studies
Procedure:
1. Repeat PT and/or APTT using patient PPP
2.
3.
4.
Run Normal Pooled Plasma alone
•
Ensure normal results or 100% of factor level
Run patient PPP mixed 1:1 with NPP
Compare results
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Initial testing is compared to mix
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Did mix correct? Did mix not correct?
PT and APTT 50:50 Mixing Studies
Interpretation:
• If the time of the 1:1 mixture result is still ≥ 10% of the pooled normal
plasma result (or outside the reference interval), no correction has
occurred and a circulating inhibitor such as lupus anticoagulant is
suspected
• If the time of the 1:1 mixture result is within ≤ 10% of the pooled
normal plasma result (or within reference intervals), a correction has
occurred and a factor deficiency or specific factor antibody may be
suspected as the cause for the cause of the originally prolonged
test(s)
Example:
Patient plasma
PT = 12s
APTT = 49s
(Normal)
(Prolonged)
Normal Pooled Plasma
APTT = 27s (Normal)
MIX APTT 1:1 (Patient:NPP)
APTT = 30s (slightly more prolonged than NPP)
•
Patient’s plasma was “Corrected” by the NPP
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NPP provided a factor that was lacking in the patient’s
sample
•
“Correction” rules out a non-specific inhibitor
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Could be an antibody to a factor (rule out by incubation)
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Could be Factor deficiency
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Further testing is then needed to identify the factor
deficiency (Factor Assay)
5 M UREA SOLUBILITY TEST
Principle:
• Performed to specifically assess FXIII deficiency
or inhibition
• FXIII is insoluble in urea
• In the absence of FXIII, fibrin clot will dissolve
rapidly in presence of urea
• Positive results should be confirmed by FXIII
assay
•
Quantitative FXIII activity assay
THROMBIN TIME (TT)
• Commercially available bovine thrombin reagent transforms
plasma fibrinogen to a detectable fibrin polymer
• Thrombin reagent and patient’s plasma (100uL) are pre-warmed at
370C for 3 min
• 200 uL of thrombin is added to patient’s plasma and chronometer
is started, clot formation is recorded
• RI: 15-20 s
• TT is prolonged when there is hypofibrinogenemia (<100mg/dL) or
afibrinogenemia or dysfibrinogenemia
• TT may be replaced by Reptilase time test (SOP the same)
PROTHROMBIN TIME (PT)
Test Procedure
1.
PT reagent is warmed to 37ºC
2.
PPP aliquot is warmed to 37ºC for 3-10 min
-
Aliquots that are incubated longer than 10
minutes become prolonged
o
Coagulation factors begin to
deteriorate or are affected by
evaporation and pH change
3.
A premeasured volume of reagent is added
(speedily) to the plasma aliquot and a timer is
started
4.
As clot forms, timer stops, and elapsed time is
recorded
5.
Fibrin clot is detectable visually or by optical or
electromechanical sensors
PROTHROMBIN TIME (PT) & INR
• Due to inherent variations in
Thromboplastin reagents from lab to lab and
in an effort to standardize inter-laboratory
PT reporting, the International Normalized
Ratio (INR) was developed
• INR standardizes PT results and reporting,
to allow for monitoring of Vitamin K
antagonist therapy (such as,
Coumadin/Warfarin) across different labs
• INR is reported along with PT result
PROTHROMBIN TIME (PT)
•
PT (in seconds) and ISI are used to calculate the INR
‒ISI = International Sensitivity Index
•
Commercial suppliers of Thromboplastin reagent
preparations supply ISI with each reagent lot
•
ISI indicates how sensitive the reagent is to
deficiencies in Vitamin K dependent factors compared
to the WHO (World Health Organization) reference
standard
PROTHROMBIN TIME (PT) & INR
ISI
INR =
Patient PT
Mean Normal PT
Mean Normal PT= The geometric mean normal PT is determined from
at least 20 fresh plasma specimens obtained from healthy individuals
PROTHROMBIN TIME (PT) & INR
•
Reference Intervals
• Manual PT: 10.6 – 14.6 s
• Automated PT: could be a bit different (e.g., 9.5 13.5 s)
• INR: 0.9 - 1.2
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•
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Varies from lab to lab
Must be re-established once a year
Report PT in Seconds & calculate INR (manual)
Automated analyzers automatically calculate
INR
ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT/PTT)
APTT – clot-based routine coagulation test
APTT is used to assess deficiencies or
inhibitors of the factors in the intrinsic and
common pathway:
•
Factors XII, XI, IX, VIII, X, V, II (prothrombin), I
(fibrinogen) – all factors except FVII
To monitor standard (unfractionated) Heparin
anticoagulant therapy
ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT/PTT)
Test Procedure
1. Equal volumes of PPP and 1st reagent- contact
activator + PL are combined and incubated for
3 minutes
2. 2nd reagent- CaCl2 is then added, the sample is
mixed while kept at 37ºC, and then timing is
started
3. Timing is stopped when first signs of a fibrin
strands are seen
4. Fibrin clot is detectable visually or by optical or
electromechanical sensors
5. RI: 25-35 s, could vary from lab to lab, must be
established once a year
NCS: can be silica, kaolin, ellagic acid, or celite
COAGULATION SAMPLE COLLECTION
Frequency of Errors
Pre-analytical
Analytical
Post-analytical
68,2
13,3
18,5
The distribution of mistakes was: preanalytical 68.2%, analytical 13.3%, and
postanalytical 18.5%. Most of the laboratory mistakes (74%) did not affect patients’
outcome. However, in 37 patients (19%), laboratory mistakes were associated with
further inappropriate investigations, thus resulting in an unjustifiable increase in
costs. Moreover, in 12 patients (6.4%) laboratory mistakes were associated with
inappropriate care or inappropriate modification of therapy (Plebani and Carraro,
Clinical Chemistry. 1997;43:8:1348 –1351).
COAGULATION SAMPLE COLLECTION
•
•
•
•
•
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Acceptable anticoagulant: 3.2% buffered Sodium Citrate,
Sodium Citrate leaves all clotting factors available except
Calcium, Citrate binds the calcium in the plasma and
therefore prevents coagulation, but not as strongly as EDTA
Plasma (contains coagulation factors) is separated from
platelets (phospholipid source) by centrifugation = PlateletPoor Plasma (PPP- platelet count <10x109/L)
Centrifugation at 3000 RPM for 15 minutes at room
temperature
9:1 blood-to-anticoagulant ratio is required for optimum
results (9 parts whole blood to 1 part sodium citrate)
High Hematocrit (≥ 55%) affects ratio
Whole blood: Anticoagulant Ratio
Adjustment for high hematocrit:
C = (1.85x10-3)(100-H) x V
C = volume of sodium citrate (mL)
V = volume of whole blood-sodium citrate solution (mL)
H = hematocrit (%)
Example:
To collect 3mL of blood and anti-coagulant mixture from a patient who’s HCT is
65%, calculate the volume of sodium citrate as follows:
C = (1.85x10-3)(100-65 %) x 3.0mL
C = (1.85x10-3)(35 %) x 3.0mL
C= 0.19 mL of 3.2% sodium citrate
CASE 1
A 55-year-old man comes to the emergency department with epistaxis. He reports that he has
“bleeder’s disease” and has had multiple episodes of inflammatory hemarthroses. Physical
examination reveals swollen, immobilized knees; mild jaundice; and an enlarged liver and spleen.
Complete blood count results indicate that the patient is anemic and has thrombocytopenia with
a platelet count of 74,400/μL. PT is within reference range and aPTT is 43 seconds.
1. What is the most likely diagnosis?
2. What treatment (s) does the patient need?
3. What reflex test (s) would you suggest?
4. What would be the result of mixing studies?
CASE 2
A 28-year-old female patient presents with excessive bleeding after a dental extraction. She
claims to suffer from very heavy menstruation, bleeding gums and recurrent nose bleeds
throughout her life. Coagulation screen results are as follows:
PT: 12.8s
APTT: 42.9s
PLT: 208 x109/L
Questions:
1. As the next step, you do mixing studies and find mix aPTT to be 35.1s, what is your
interpretation?
2. Can this be due to a lupus anticoagulant?
3. Considering the laboratory results, history, and patient’s gender, suggest the most likely
clinical condition
4. List any investigation studies used to detect this suggested clinical condition and their
respective results
CASE 3
A 35-year-old female patient
is in the ICU with sepsis after
a cesarean section.
CBC
• WBC: 2.3 x109/L
• RBC: 3.2 x1012/L
• HGB: 100 g/L
• HCT: 0.30 L/L
Questions:
• MCV: 93 fL
1.
• MCH: 32 pg
2.
3.
Describe the peripheral blood
findings
What additional tests should be
performed and list the expected
results?
Based on all the data provided,
what clinical condition is most
likely?
• MCHC: 345 g/L
• RDW: 17.9 %
• PLT: 10 x109/L
Manual Differential:
•
Neutrophils: 90
•
Lymphocytes:10
•
Monocytes: 0
•
Eocinophils: 0
•
Basophils: 0
NRBCs- 9/100
Many Band cells seen
Marked toxic granulation
RBC Morph:
•
Many schistocytes