Lecture Activities

PLT size

9-13 fl

what is the job of the glycocalyx

Their function is to protect the platelet, aid in adhesion, and plays a role in immune regulation.

what kinds of granules are in PLTs

alpha granules

dense granules

dense granule materials

ADP

ATP

Calcium

Magnesium

serotonin

What are the 3 Steps in Primary Hemostasis?

Adhesion

Aggregation

Secretion

What are the 4 stages of platelets in Primary Hemostasis?

Endothelial Injury

Exposure

Activation

Aggregation

Please list the 5 items that are secreted by activated platelets

Serotonin

Calcium

Thromboxane

Von Willebrand factor

ADP

main receptor on PLT for primary hemostasis

GP1b

what does thrombin do (4)

Activating PLT

Cleaves fibrinogen to fibrin

Cleaves stabilizing factor

Activated cofactors

List the 4 key anticoagulants (naturally occurring)

Antithrombin III

Heparin Cofactor HCII

Protein C and Protein S (PC,PS)

Cell regulators

Who releases tPA?

Normal healthy cells release small amounts of tPA naturally

What is the stimulus for tPA release?

When healthy tissue is exposed to FX and thrombin they are stimulated to produce more tPA

fibrinolytic cascade

fibrin polymer + XIIIa leads to cross linked fibrin clot

PAi turns to tPA.

tPA cleaves plasminogen to plasmin

plasmin degrades the crosslinked fibrin clot

How does Heparin work?

Heparin indirectly inhibits clotting factors by binding to and increasing the activity of ATIII (antithrombin III)

Is heparin a direct thrombin inhibitor or a FX inhibitor?

FX inhibitor

how does aspirin work

blocks the synthesis of thromboxane A2 which means the enzyme cannot produce thromboxane. Targets the activation step

how do ADP receptors inhibitors work

blocks PLT aggregation by interfering with ADP which blocks GPIIB/IIIA expression. Blocks aggregation. Targets the activation step

how do GPIIB/IIIA inhibitors work?

antibodies that bind to the GPIIB/IIIA receptor which prevents the PLT from crosslinking with fibrinogen and other platelets. Targets the aggregation step.

INR calculation

(PTtest / PTnormal) ^ISI

Where do you find the ISI?

ISI is found in the standards set by each manufacturer or lab for the tissue factor. This allows comparison of tissue factor from batch to batch

what do TEG/TEM test?

Tests for extrinsic pathway, intrinsic pathway, fibrinogen, clotting time, strength of clotting, and how the clot is lysed.

when is TEG/TEM useful?

cardiothoracic patients to see what they need from the blood that they receive from the blood bank.

Helpful in cases of large blood volume loss and clotting issues to inform what product to give the patient.

More commonly used in emergency medicine when we don't have much time.

A Platelet function screen is useful for identifying what types of coagulopathies?

Abnormal results may indicate Von Willebrand disease, Glanzmann's, or Bernard Soulier disease. Tells us the patient has a platelet disease!

What are some KEY symptoms of Primary Hemostatic Problems?

Pethechiae

Anterior epistaxis

Prolonged bleeding time

Decreased PLT number

Decreased PLT function

What are KEY symptoms of Secondary Hemostatic Problems?

Ecchymoses

Deep tissue hematoma

Posterior epistaxis

Prolonged PT

Prolonged PTT

Decreased clotting factors

main symptoms of vWD

Mucocutaneous bleeding

Deep tissue bleeding

difference between type 1 and type 2 vWD

Type 1: low number vWF

Type 2: abnormal number of vWF and abnormal function

vWD PLT aggregation study

decreased

Bernard Soulier: What is the deficiency here?

Deficiency or absence of PLT receptor (Gp1b)

Glanzmann Thrombasthenia: what is the deficiency here?

GP2b3a

Uremic Platelet Dysfunction: what organ is at fault here?

kidney

what gene is responsible for TTP

ADMTS-13

symptoms of TTP

Thrombocytopenia (low PLT)

Microangiopathic hemolytic anemia (MAIHA)

Fever

Renal insufficiency (hematuria, decreased urine output)

Neurological issues (headache and confusion)

what would we see on a blood smear from a patient with TTP

schistocytes due to MAIHA

how are DIC and TTP similar

both can result in MAIHA

how are DIC and TTP different

DIC PT and PTT are prolonged

TTP PT and PTT are normal

common lab values in DIC

Prolonged PT and PTT

Thrombocytopenia

MAIHA

Decreased fibrinogen

Increased D-Dimer

pattern of clotting and bleeding for DIC

Initially the patient is more likely to clot

Later the patient is more likely to bleed.

etiology of HIT

•  IgG Ab complexes with heparin and PLT factor 4, activating it

ITP pathogenesis

Autoantibodies that target PLT for destruction by binding to GP2b3a

Primary ITP vs Secondary ITP

• Primary ITP = ITP alone

• Secondary ITP = ITP triggered by Hep C, HIV, or lupus

what is the deficiency in hemophilia A

factor VIII

what is the deficiency in haemophilia B

factor IX

what is the deficiency in haemophilia C

factor XI

symptoms of haemophilia C

physical findings are relatively normal except when bleeding occurs, bruising may occur at unusual sites, pallor, fatigue, tachycardia

genetic link in haemophilia C

not X linked!

seen in both males and women

How does Liver Disease affect the coagulation process?

The liver is where coagulation factors are made except VIII

5 MAIN Thrombophilia diseases

Factor V Leiden

Prothrombin gene mutation

Protein C deficiency

Protein S deficiency

Antiphospholipid syndrome

what causes the issue with factor V leiden

autosomal dominant point mutation in the gene for factor V

what causes PC and PS deficiency

vitamin K deficiency due to warfarin

The primary inhibitor of the fibrinolytic system is:

antiplasmin

Dilute Russell's viper venom test (DRVVT) is helpful in the diagnosis of:

lupus anticoagulant

Warfarin (Coumadin) acts on what?

It acts on Vitamin K-dependent clotting factors

Protein C Function

It is a physiologic inhibitor of coagulation

Thrombin-thrombomodulin complex is necessary for:

activation of protein C

Heparin-induced thrombocytopenia is caused by:

antibody to heparin-platelet factor 4 complex

Which of the following results are correct regarding lupus inhibitors?

prolonged aPTT on undiluted plasma because the PTT pathway includes phospholipids (Anti-phos)

The APTT is sensitive to a deficiency of which clotting factor?

A. Factor VII

B. Factor X

C. PF3

D. Calcium

B. Factor X

B The APTT is sensitive to the deficiency of coagulation factors in the intrinsic pathway (factors XII, XI, IX, and VIII) and the common pathway (factors X, V, II, and I).

A patient with a prolonged PT is given intravenous vitamin K. The PT corrects to normal after 24 hours. What clinical condition most likely caused these results?

A. Necrotic liver disease

B. Factor X deficiency

C. Fibrinogen deficiency

D. Obstructive jaundice

D. Obstructive jaundice

D Obstructive jaundice contributes to coagulation disorders by preventing vitamin K absorption. Vitamin K is fat soluble and requires bile salts for absorption. Parenteral administration of vitamin K bypasses the bowel; hence the need for bile salts.

A prolonged APTT is corrected with factor VIII- deficient plasma but not with factor IX-deficient plasma. Which factor is deficient?

A. V

B. VIII

C. IX

D. X

C. IX

C Because the prolonged APTT is not corrected with a factor IX-deficient plasma, factor IX is suspected to be deficient in the test plasma.

Refer to the following results:

PT = prolonged

APTT = prolonged

Platelet count = decreased

Which disorder may be indicated?

A. Factor VIII deficiency

B. von Willebrand's disease

C. DIC

D. Factor IX deficiency

C. DIC

C In DIC, there is a diffuse intravascular generation of thrombin and fibrin. As a result, coagulation factors and platelets are consumed, resulting in decreased platelet count and increased PT and APTT.

Which of the following is a predisposing condition for the development of DIC?

A. Adenocarcinoma

B. Idiopathic thrombocytopenic purpura (ITP)

C. Post-transfusion purpura (PTP)

D. Heparin-induced thrombocytopenia (HIT)

A. Adenocarcinoma

A Adenocarcinoma can liberate procoagulant (thromboplastic) substances that can activate prothrombin intravascularly. ITP is a thrombocytopenia caused by an autoantibody; PTP is an alloimmune thrombocytopenia caused by transfusion of blood or blood products; HIT results from an antibody to heparin-PF4 complex causing thrombocytopenia in 1%-5% of patients who are on heparin therapy. In some affected persons, thrombosis may also occur.

Factor XII deficiency is associated with:

A. Bleeding episodes

B. Epistaxis

C. Decreased risk of thrombosis

D. Increased risk of thrombosis

D. Increased risk of thrombosis

D Factor XII-deficient patients commonly have thrombotic episodes. Factor XII is the contact activator of the intrinsic pathway of coagulation. It also plays a major role in the fibrinolytic system by activating plasminogen to form plasmin. Hemorrhagic manifestations are not associated with factor XII deficiency because thrombin generated by the extrinsic pathway can activate factor XI to XIa, and factor VIIa/TF can activate factor IX to IXa

The following laboratory results were obtained from a 40-year-old woman:

PT = 20 sec; APTT = 50 sec; thrombin time = 18 sec.

What is the most probable diagnosis?

A. Factor VII deficiency

B. Factor VIII deficiency

C. Factor X deficiency

D. Hypofibrinogenemia

D. Hypofibrinogenemia

D Fibrinogen (factor I) is a clotting protein of the common pathway and is evaluated by the thrombin time. In hypofibrinogenemia (fibrinogen concentration <100 mg/dL), the PT, APTT, and TT are prolonged. In factor VII deficiency, the APTT is normal; in factor VIII deficiency, the PT is normal; and in factor X deficiency, the TT is normal.

When performing a factor VIII activity assay, a patient's plasma is mixed with:

A. Normal patient's plasma

B. Factor VIII deficient plasma

C. Plasma with a high concentration of factor VIII

D. Normal control plasma

B. Factor VIII deficient plasma

B Coagulation factor assays are based upon the ability of the patient's plasma to correct any specific factor-deficient plasma. To measure for factor VIII activity in a patient's plasma, diluted patient plasma is mixed with a factor VIII-deficient plasma. An APTT test is performed on the mixture. Each laboratory should calculate its own normal ranges based on patient population, reagents, and the instrument used. An approximate range of 50%-150% is considered normal.

Refer to the following results:

PT = normal

APTT = prolonged

Bleeding time= increased

Platelet count = normal

Platelet aggregation to ristocetin = abnormal

Which of the following disorders may be indicated?

A. Factor VIII deficiency

B. DIC

C. von Willebrand's disease

D. Factor IX deficiency

C. von Willebrand's disease

C VWF is involved in both platelet adhesion and coagulation via complexing with factor VIII. Therefore, in von Willebrand's disease (deficiency or functional abnormality of VWF) factor VIII is also decreased, causing an abnormal APTT as well as abnormal platelet aggregation to ristocetin. The platelet count and the PT are not affected in VWF deficiency

Fibrin monomers are increased in which of the following conditions?

A. Primary fibrinolysis

B. DIC

C. Factor VIII deficiency

D. Fibrinogen deficiency

B. DIC

Which of the following is associated with multiple factor deficiencies?

A. An inherited disorder of coagulation

B. Severe liver disease

C. Dysfibrinogenemia

D. Lupus anticoagulant

B. Severe liver disease

B Most of the clotting factors are made in the liver. Therefore, severe liver disease results in multiple factor deficiencies. An inherited disorder of coagulation is commonly associated with a single factor deficiency. Lupus anticoagulant is directed against the phospholipid-dependent coagulation factors. Dysfibrinogenemia results from an abnormal fibrinogen molecule

Normal PT and APTT results in a patient with a poor wound healing may be associated with:

A. Factor VII deficiency

B. Factor VIII deficiency

C. Factor XII deficiency

D. Factor XIII deficiency

D. Factor XIII deficiency

D Factor XIII deficiency can lead to impaired wound healing and may cause severe bleeding problems. Factor XIII is a fibrin stabilizing factor that changes the fibrinogen bonds in fibrin polymers to stable covalent bonds. Factor XIII is not involved in the process of fibrin formation and, therefore, the PT and APTT are both normal

Fletcher factor (prekallikrein) deficiency may be associated with:

A. Bleeding

B. Thrombosis

C. Trhombocytopenia

D. Thrombocytosis

B. Thrombosis

B Fletcher factor (prekallikrein) is a contact factor. Activated prekallikrein is named kallikrein and is involved in activation of factor XII to XIIa. Like factor XII deficiency, Fletcher factor deficiency may be associated with thrombosis.