Download MBBS Physiology Presentations 45 Blood Cells Platelets Lecture Notes

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Blood cells ? Platelets (Thrombocytes)

Learning Objectives

Platelets Morphology

Hemostasis

Primary hemostasis

Platelet plug formation

Disorders of primary hemostasis

Secondary hemostasis

Disorders of secondary hemostasis

Tests to assess hemostasis

Anticoagulants


PlateletsCharacteristics

Small 23 ?m discshaped, anuclear, reddishpurple

cells.

Platelet life span 710 days

Platelets count: 1.54 lakh/ mm3 of blood

(Platelets are released from bone marrow to enter

2/3 peripheral blood and 1/3 seized in spleen.)

Platelets-Production

& IL3

Platelets are formed within the cytoplasm of

megakaryocytes (1 megakaryocyte produces

about 2000 platelets)within bone marrow

and released into the circulation.


Platelets structure

Peripheral zone:

Responsible for platelet adhesion and aggregation

Glycocalyx: Fluffy surface coat contains

glycoprotein receptors: GPIa & IIa binds to col agen,

GPIb binds von Wil ebrand's factor ; GPIIb/IIIa binds fibrinogen

Membrane Zone

Layer cal ed PF3 (platelet factor) surface for interaction

of plasma coagulation factors, Initiation of formation of

thromboxane A2

2 systems :Surface-connected open canalicular system (OCS)

Dense tubular system(DTS).

Cytoskeleton
Responsible for platelet retraction and platelet shape
Microtubules/Microfilaments
Binding proteins: Actin & Myosin
Organelle zone
Responsible for storage and platelet release functions
Granules:Dense bodies, alpha granules, lysosomal granules and microperoxisomes. Mitochondria and Glycogen.

Hemostasis

Hemostasis is the natural process that stops blood loss when an injury occurs. It involves three steps that

occur in a rapid sequence:

Primary Hemostasis: (1) vascular spasm, or vasoconstriction, a brief and intense contraction of blood

vessels; (2) formation of a platelet plug; and

Secondary Hemostasis: blood clotting or coagulation, which reinforces the platelet plug with fibrin mesh

that acts as a glue to hold the clot

fibrinolytic proteins system - Excessive blood clotting is prevented.


Primary Hemostasis - Vasoconstriction

Vasoconstriction

The vasoconstriction that occurs during hemostasis

is a brief reflexive contraction that causes a

decrease in blood flow to the area and restrict

blood loss.

The vasoconstriction response is triggered by

factors such as secretion of serotonin from

activated platelets, a direct injury to vascular

smooth muscle and nervous system reflexes

initiated by local pain receptors.

Platelets Function- Pri. Hemostasis - Platelets plug formation

Platelets plug formation

1) Adhesion ? exposed collagen (GpIa & GpIIa and vWF-GpIb)

2) Activation ?Initiation of formation of thromboxane A2 and secretion of granule contents specially

ADP & Ca++

3) Aggregation - Expression of GpIb-IIIa receptors on platelets to glue together


Formation of thromboxane A2 and Antiplatelet activity of Aspirin


(ASPIRIN)

Thromboxane synthetase

Platelets Function- Pri. Hemostasis - Platelets plug formation


Abnormalities in primary hemostasis-Purpura

Purpura is purple-colored spots and patches that

occur on the skin, and in mucus membranes,

including the lining of the mouth. Purpura occurs

when small blood vessels leak blood under the skin.

Purpura measure between 4 and 10 mm

(millimeters) in diameter. When purpura spots are

less than 4 mm in diameter, they are called

petechiae. Purpura spots larger than 1 cm

(centimeter) are called ecchymoses.

Abnormalities in primary hemostasis

Defects in the blood vessel wall- lead to hemorrhage from mucosal surfaces (epistaxis, gingival bleeding, melaena,

haematuria), and into skin and mucosae (petechial or ecchymotic haemorrhages - Purpura).


Decreased platelets number (Thrombocytopenia) or function (Thrombosthenia)

Abnormal vWF- Bernard Soulier Syndrome

Primary haemostasis inhibitors - natural inhibitors of platelet function - such as prostacyclin, bradykinin released by

endothelial cells.

Induced inhibition of platelet function - more commonly, platelet function is inhibited intentional y by the

administration of agents such as aspirin for the prevention of thrombosis.


Causes of Thrombocytopenia

Bone Marrow Dysfunction ?Many conditions and factors can damage stem cells

Cancer- leukemia or lymphoma. Cancer treatments, such as radiation and chemotherapy.

Toxic Chemicals- pesticides, arsenic, and benzene

Medicines-diuretics and chloramphenicol (aspirin or ibuprofen, also can affect platelets functioning)

Alcohol-especial y if they're eating foods that are low in iron, vitamin B12, or folate.

Viruses-Chickenpox, mumps, rubel a, Epstein-Barr virus, HIV and dengue fever virus etc often develop thrombocytopenia.

Genetic Conditions-Wiskott-Aldrich syndromes.

The Body Destroys Platelets at a higher rate

ITP (Idiopathic thrombocytopenic purpura)

Autoimmune Diseases-immune thrombocytopenia . An autoimmune response is thought to cause most cases of ITP eg

SLE and RA

Margination in congestive splenomegaly

Medicines-quinine; antibiotics that contain sulfa; dilantin, vancomycin, and rifampin.

Infection-a widespread bacterial infection septicemia, mononucleosis or cytomegalovirus

Surgery-Prosthetic heart valves, blood vessel grafts, or machines and tubing used - blood transfusions or bypass surgery.

Pregnancy-About 5 percent of pregnant women develop mild thrombocytopenia when they're close to delivery.

Process of secondary hemostasis-Blood Coagulation-Clotting Factors


Process of secondary hemostasis-Blood Coagulation

Disorders of Blood Coagulation- Coagulopathy

Coagulopathy is a condition in that the blood's ability to coagulate is

impaired. This condition can cause a tendency toward prolonged or

excessive bleeding (bleeding diathesis), which may occur

spontaneously or following an injury
Disorders of Blood Coagulation- Hypocoagulopathy -CAUSES

Major causes of coagulation disorders resulting in bleeding include:

?Hemophilia-Factor VIII deficiency (X chromosome linked disorder)

?Von Willebrand disease

?Other clotting factor deficiencies (Christmas disease)

?Disseminated intravascular coagulation

?Liver Disease

? Vit K deficiency

Disorders of Blood Coagulation- Hyper-coagulopathy - CAUSES

?Conditions increasing the risk of a blood clot:

?Inherited (genetic) abnormalities that cause an increased tendency to clot

?A surgical procedure

?Sitting or lying down for long periods (more than 4 hours)- for example, after surgery

or on long plane or car rides. This lack of movement reduces blood flow in the legs by

50%.

?Major injury

?Increasing age

?Cancer

?Heart failure

?Pregnancy

?Use of hormone therapy such as birth control pills or hormone replacement therapy

?Having a history of DVT

?Tobacco


Fibrinolytic System

Process of Thrombosis & Bleeding (fibrinolysis) should be balanced

Clotting factor deficiencies may cause the

development of a significant bleeding tendency.

Formation of clots inside blood vessels is called

thrombosis due to hyper coagulability of blood

Thromboses are a major medical problem.

They frequently occlude the arterial supply to the

organs in which they form, and bits of thrombus

(emboli) sometimes break off and travel in the

bloodstream to distant sites, damaging other organs.

An example is obstruction of the pulmonary artery or

its branches by thrombi from the leg veins

(pulmonary embolism).
Tests of Hemostasis-Laboratory Investigations

Capil ary Fragility Test ? The test is defined by the WHO as one of the necessary requisites for diagnosis of Dengue fever. ? A

blood pressure cuff is applied and inflated to a point between the systolic and diastolic blood pressures for five minutes. ?

The test is positive if there are 10 or more petechiae per square inch. ? In DHF the test usual y gives a definite positive result

with 20 petechiae or more. Indicative of hemorrhagic tendency of a person

Platelet Count ? Platelet Count can be determined by improved Neubauer's counting chamber with RBC pipette & 1%
ammonium oxalate. ? They can be seen as tiny diameter, well seprated, highly refractile rounded bodies with silvery
appearance. ? N : 1.5 ? 4 lacs / cumm. ? Leishman stain : in clumps, blue cytoplasm, reddish purple granules, no nucleus. ?
Surgical bleeding usual y does not occur until the platelet count is less than 50,000/mm3. ? Spontaneous bleeding does not
occur until the platelet count is less than 10,000-20,000/mm3. Platelet Count ? THOMBOCYTOPENIA : ? Bone marrow
depression ? Aplastic anemia ? Hypersplenism ? Viral infections ? Drugs : Aspirin, Heparin, Chemotherapy ? ITP ? TTP ?
DIC

Bleeding Time ? It is the time taken from the puncture of the blood vessel to the stoppage of bleeding. N : 1-6 minutes

? The bleeding time test is a useful tool to test for platelet plug formation and capil ary integrity.

? BT is more imp. than CT.

? CT concerns the blood only i.e. how firm the clot is formed, whereas BT involves the interaction of blood with injured

tissues.

? People with von Wil ebrand disease usual y experience increased bleeding time. ? Von Wil ebrand factor is a platelet

agglutination protein, but this is not considered an effective diagnostic test for this condition.

Tests of Hemostasis-Laboratory Investigations

Clotting Time It is the time taken from the puncture of the blood vessel to the formation of a fibrin thread. ? A. Capil ary Glass

Tube Method : Here the blood is collected in capil ary tube & total time is noted to form FIBRIN THREADS on breaking tube

every 30 seconds. N : 3-8 minutes ? Mechanism Involved is INTRINSIC Pathway. ? CT depends on presence of all clotting

factors. ? It gets prolonged in : - 1. Deficiency of clotting factors ? Hemophilia. - 2. Vitamin K Deficiency ? Factor II, VII, IX

& X. - 3. Anticoagulant overdose. ? BT & CT is measured before surgery & liver or bone marrow biopsy. ? PURPURA : BT

increased, CT normal. ? HEMOPHILIA : BT normal, CT increased.

Prothombin Time ? The prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international normalised

ratio (INR) are measures of the extrinsic pathway of coagulation. ? They are used to determine the clotting tendency of blood, in

the measure of warfarin dosage, liver damage and vitamin K status. ? PT measures factors I, II, V, VII and X. ? The reference

range for prothrombin time is usually around 11-16 seconds; the normal range for the INR is 0.8?1.2.

APTT ? The partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT or APTT) is a performance

indicator measuring the efficacy of both the intrinsic and the common coagulation pathways. ? Apart from detecting

abnormalities in blood clotting, it is also used to monitor the treatment effects with heparin, a major anticoagulant. ? Normal

PTT times require the presence of the following coagulation factors: I, II, V, VI I, IX, X, XI & XII. ? Deficiencies in factors VI or

XII wil not be detected with the PTT test.
ANTICOAGULANTS

Heparin is a naturally occurring anticoagulant

that facilitates the action of anti-thrombin III. Low-molecular weight fragments with an average molecular weight

of 5000 have been produced from unfractionated heparin, and these low-molecular-weight heparins are seeing

increased clinical use because they have a longer half-life and produce a more predictable anticoagulant

response than unfractionated heparin.

In vivo, a plasma Ca2+ level low enough to interfere with blood clotting is incompatible with life, but clotting can

be prevented in vitro if Ca2+ is removed from the blood by the addition of substances such as oxalates, which

form insoluble salts with Ca2+, or chelating agents, which bind Ca2+. Used in vitro only.

Coumarin derivatives such as dicumarol and warfarin are also effective anticoagulants. They inhibit the

action of vitamin K, which is a necessary cofactor for the enzyme that catalyzes the conversion of glutamic acid

residues to -carboxyglutamic acid residues. Six of the proteins involved in clotting require conversion of a

number of glutamic acid residues to -carboxyglutamic acid residues before being released into the circulation,

and hence all six are vitamin K-dependent. These proteins are factors II (prothrombin),VII, IX, and X, protein C,

and protein S.

Self Assessment

Megakaryocyte produces about ..........................platelets.

Platelet life span ....................... Days.

...............................receptors causes gluing of platelets together.

? Spontaneous bleeding does not occur until the platelet count is less than

........................../mm3.

? Surgical bleeding does not occur until the platelet count is less than

.................................../mm3.

? Secondary Hemostasis includes ....................................processes.

? Liver Disease results in hyp0coagulability of blood because...........................
Thank you

This post was last modified on 08 April 2022