N245: Disorders of Hemostasis & Erythrocytes

Hemostasis

To stop or control bleeding; the "halting of blood"

What are the two main steps of hemostasis?

1. Clot formation

2. Clot dissolution

What three components enable hemostasis?

Thrombocytes, the coagulation system, and vascular endothelial cells

Thrombocytes

Non-nucleated fragments of the cytoplasm of megakaryocytes

Where are platelets stored?

1/3 are stored in the spleen

Where do platelets come from?

Megakaryocytes in the bone barrow --> their cytoplasm breaks apart and forms platelets

What triggers the production of platelets?

Thrombopoietin (TPO), which is synthesized in the liver, kidneys and bone marrow

Coagulation system

Clotting cascade --> extrinsic/intrinsic pathways -->

each activated factor catalyzes the next reaction --> fibrin clot

Plasma clotting factors

Substances that promote coagulation; remain inactive in blood until activated --> clotting cascade

Example: Factor X

Natural anticoagulants

Prevent excess coagulation; inactivate clotting factors --> interrupts clotting cascade

Examples: Protein C and S, Plasmin

Intrinsic Pathway

Slow process; activated by an injury inside the blood vessel --> clotting factors are present within the blood and are activated by exposed collagen fibers

Extrinsic pathway

Fast process; activated by injury outside the blood vessel --> clotting factors are located outside the blood and are activated by exposure to tissue factor

Terminal steps of extrinsic pathway

1. Activation of factor X

2. Xa converts prothrombin to thrombin

3. Thrombin converts fibrinogen to fibrin

4. Fibrin strands stabilize the clot

Vascular Endothelial Cells

Squamous cells that line walls of blood vessels

What roles do Vascular Endothelial Cells play in hemostasis?

1. Synthesize and secrete procoagulant factors

2. Prevent the formation of blood clots

Von Willebrand factor (vWf)

A protein synthesized by Vascular Endothelial Cells --> promotes platelet adhesion

Prostacyclin and NO

Proteins released by Vascular Endothelial Cells --> they prevent platelet adhesion

Thrombin inhibitors

Proteins released by Vascular Endothelial Cells, they inhibit thrombin --> interrupts the coagulation pathway --> prevents the formation of a clot

Tissue plasminogen activator (tPA)

Proteins released by Vascular Endothelial Cells, it converts plasminogen to plasmin --> which breaks down the fibrin strands in a blood clot

Stages of hemostasis

1. Vasoconstriction

2. Platelet plug formation

3. Blood coagulation

4. Clot retraction

5. Clot dissolution

Vasoconstriction

What: The narrowing of blood vessels

Why: Neural reflexes, thromboxane A2 (TXA2) released by the platelets

Platelet plug formation

What: Platelets stick together at the injury site

Why: Vascular Endothelial Cells release vWf --> platelets adhere to the exposed collagen --> platelets secrete ADP and TXA2 --> attract more platelets

Blood coagulation

What: The formation of a blood clot

Why: Intrinsic or extrinsic pathway --> factor X --> prothrombin to thrombin --> fibrinogen to fibrin

Step one of coagulation

Factor X is activated by either intrinsic or extrinsic pathway

Step two of coagulation

Prothrombin is converted into the active enzyme thrombin

Step three of coagulation

Thrombin converts fibrinogen to fibrin --> fibrin strands trap RBCs in a jelly substance

Clot retraction

What: The tightening of the fibrin clot

Why: Fibrin strands between the platelets shrink, pulling the two sides of the fissure closer to each other --> clot tightens

Clot dissolution

What: The clot dissolves (fibrinolysis)

Why: Tissue plasminogen activator (tPA) released by the injured tissues --> converts plasminogen to plasmin --> digests the fibrin strands

Hemostatic Disorders

Bleeding and clotting abnormalities

Hypercoagulability states

Conditions that increase clot formation within arteries or veins

Arterial thrombi

Blood clots in the superficial or deep arteries

How does atherosclerosis lead to arterial thrombi?

Deposits of cholesterol and fats in the arteries --> platelets stick to them --> clot forms

How can a splenectomy lead to arterial thrombi?

1/3 of platelets are stored in the spleen --> removal of spleen --> platelets have NO HOME ANYMORE!! --> high platelet count in blood --> thrombocytosis

Venous thrombi

Blood clots in the superficial or deep veins

How can prolonged immobilization lead to venous thrombi?

Long periods of sitting --> blood pools in the veins the legs

This happened to poor Hailey Bieber on the plane and then she had a stroke!

How can pregnancy lead to venous thrombi?

Pregnancy increases the level of plasma clotting factors --> increased risk for thrombi

Superficial thrombophlebitis

Inflammation and clot formation in superficial veins, usually in the leg

Deep vein thrombosis (DVT)

A blood clot in a deep vein, most often in legs

Bleeding disorders

Conditions that result in abnormal bleeding due to the failure of clot formation

Why do bleeding disorders occur?

1. Decrease in thrombocyte count

2. Issues with coagulation system

3. Weakened blood vessels

Thrombocytopenia

Definition: An abnormal decrease in thrombocytes

Causes: Decreases in platelet production, reduced platelet survival, enlarged spleen

Where does spontaneous bleeding occur?

Mucous membranes, under the skin

Purpura

Purple areas of bruising under the skin

Petechiae

Pinpoint hemorrhages under the skin

Von Willebrand Disease

Bleeding disorder caused by a deficiency of von Willebrand factor

NORMALLY, vWf is produced by the blood vessels and reacts with platelets to form a plug --> clot formation

How is Von Willebrand Disease diagnosed?

Usually diagnosed by accident (when surgery or tooth extraction results in prolonged bleeding)

S+S of von Willebrand Disease

Easy bruising, heavy periods, nosebleeds

Type 1 VWD

Person has lower than normal levels of vWf (mildest form)

Type 2 VWD

Person has normal levels of vWf, but it's structure or function is abnormal

Type 3 VWD

Person has very little or no vWf (severest form)

Hemophilia

An X-linked recessive disorder; blood fails to clot properly --> leading to excessive bleeding if injured

Hemophilia A

Factor VIII (8) deficiency --> clotting cascade is interrupted

The letter "A" rhymes with "eight"

Hemophilia B

Factor IX (9) deficiency --> clotting cascade is interrupted

Be mine B9 idk

How is hemophilia diagnosed?

Spontaneous bleeding occurs in the hip, knee, and ankle joints when a child begins to walk

Hemarthrosis

Recurrent bleeding into joint spaces (the classic symptom of hemophilia)

Nonthrombocytopenic Purpura

Bleeding disorder that results from weakened/damaged blood vessels

How can scurvy lead to Nonthrombocytopenic Purpura?

Vitamin C is needed for collagen formation --> lack of collagen leads to weak blood vessels

How can vasculitis lead to Nonthrombocytopenic Purpura?

Inflammation of blood vessels allows pathogens into blood stream --> bacteria/viruses can directly injure blood vessel walls --> causing bleeding

S+S of Nonthrombocytopenic Purpura

Easy bruising, purpura, petechiae, NORMAL platelet count

DIC

Disseminated intravascular coagulation

What is DIC?

Simultaneous, excessive clot formation AND clot dissolution; life-threatening emergency!!

Stage 1 of DIC

Injury/surgery/cancer --> intrinsic/extrinsic pathway activated --> excessive formation of clots

Stage 2 of DIC

Excessive formation of clots --> platelets and clots are used up quickly --> excess bleeding in internal/external organs

Why is the structure of RBCs unique?

The non-nucleated, biconcave disk allows for more room for hemoglobin --> more oxygen

Spectrin and ankyrin

Proteins that help maintain the shape and structure of RBCs

Erythrocytes

Red blood cells

Hemoglobin

The protein that RBCs are composed of

Structure of hemoglobin

2 alpha chains, 2 beta chains, heme groups in the middle of each

Erythropoiesis

The production of red blood cells

What stimulates erythropoiesis?

Erythropoietin (EPO), a colony-stimulating factor synthesized in the kidneys

What stimulates erythropoietin to be released?

Hypoxia (low oxygen in the blood)

Erythroblasts

Immature red blood cells in the bone marrow (nucleated)

Reticulocytes

Immature red blood cells in the blood (non-nucleated)

Life span of a RBC

120 days (4 months)

Bilirubin

A yellow pigment; formed by the breakdown of the heme group of hemoglobin when red blood cells are destroyed --> released by liver in bile

Unconjugated bilirubin (indirect)

Bilirubin circulating in the blood attached to plasma proteins --> insoluble

Conjugated bilirubin (direct)

Unconjugated bilirubin + glucuronic acid --> water soluble --> excreted in urine and bile

Jaundice

A yellowing of the skin and sclera; caused by excess bilirubin in the blood

Icterus

Jaundice

Why does jaundice occur?

Excess destruction of RBC --> causing a buildup of bilirubin

Anemia

A deficiency in the oxygen carrying capacity of RBCs

What are the three main causes of anemia

Low RBCs count, low hemoglobin, or a combination of both

Why does anemia cause fatigue/pallor?

Lack of hemoglobin (red pigment) --> low oxygen and pale skin

Why does anemia cause jaundice?

Excessive destruction of RBCs --> hyperbilirubinemia, jaundice, and pigment gallstones

Why does anemia cause tachycardia?

Low oxygen --> body increases heart rate to compensate

MCV

Mean corpuscular volume

What is MCV?

The average volume and size of individual red blood cells

Microcytic anemia

Anemia characterized by small RBCs (caused by iron deficiency)

Normocytic anemia

Anemia characterized by normal RBCs --> therefore anemia is caused by a low number RBCs

Macrocytic anemia

Anemia characterized by large RBCs (caused by B12 or Folic Acid deficiency)

Iron-deficiency Anemia

Anemia resulting when there is not enough iron to build hemoglobin for RBCs --> small (microcytic) and pale (hypochromic) RBCs

Me af

Causes of Iron-deficiency Anemia

1. Dietary deficiency (ex: veganism)

2. Bleeding (ex: heavy periods)

3. Increased iron demands (ex: adolescence)

Pica

An abnormal craving for nonfood substances (dirt, paint, or clay, ice)

Whenever I'm on my period ALL i want is ice

Koilonychia

Spoon nails, seen in severe iron deficiency

How do you prevent iron-deficiency anemia?

Increase dietary intake, use iron-fortified baby formula

How do you treat iron-deficiency anemia?

Iron supplements, eat vitamin C (helps iron absorption), blood transfusion

Megaloblastic Anemia

Anemia in which the red blood cells are larger than normal

Pathogenesis of Megaloblastic Anemia

Impaired RBC DNA synthesis --> large, immature RBCs are released into the circulation

Causes of Megaloblastic Anemia

B12 or Folic Acid deficiency (both of these vitamins are required for DNA synthesis)

Glossitis

Inflammation of the tongue, seen in severe Megaloblastic Anemia