UNIT IV: Drugs Affecting Hematology

System
 Objectives

By the end of presentation students will be able to:

• Describe uses and effects of drugs affecting haematology
system
• Describe the classification of drugs used in hematology
disorders
• Discuss the action of haematology drugs on the body
• Identify the expected and adverse reactions of drugs affecting
haematology system
• Discuss the nursing responsibility related to drugs affecting
haematology system
• Calculate the drugs dosage accurately.
 Hematologic
• There are numerous drugs
agents utilized to maintain, preserve and
restore circulation.
• The three important dysfunction of blood are thrombosis,
bleeding and anemia are commonly treated with various
agents.
• The common ones that nurses must REVIEW are the:
– Anticoagulants
– Antiplatelet
– Thrombolytic
– Anti-hyperlipidemics
– Anti-anemics
– Drugs to treat bleeding
 Blood Components

• Erythrocytes
• Leukocytes
• Platelets
• Plasma
 Platelets

• Platelets, also called thrombocytes.

• Their function is to stop bleeding by forming a clot.
• The normal platelet count is 150,000-450,000 per
microliter of blood.
 What is coagulation of blood?
• Coagulation or clotting is the process by which blood
forms clots.
• Clot: Clot is a gel-like mass formed by platelets and
fibrin in the blood.
• Clotting factors and anticoagulants are made in the
liver. They have the ability to turn on or turn off as
needed.
 What is Thrombosis?

• Coagulation or clotting of the blood in a part of the

circulatory system is thrombosis.
• The formation or presence of a blood clot in a blood
vessel. The vessel may be any vein or artery as, for
example, in a deep vein thrombosis or a coronary
(artery) thrombosis. The clot itself is termed
a thrombus.
 What is embolism?

• An embolism is the sticking of an embolus in blood

vessel. The embolus may be a blood clot (thrombus),
a fat globule (fat embolism), a bubble of air or other
gas (gas embolism), or foreign material.
 Important to know
• Prothrombin: Prothrombin is a protein produced by the liver.
Prothrombin is present in blood plasma that is converted into
active thrombin during coagulation.
• Prothrombin is converted into thrombin by a clotting factor
known as factor X or prothrombinase.
• Function of Thrombin: it is an enzyme that causes the clotting of
blood by converting fibrinogen to fibrin
• Prothrombin activator: Prothrombin activator is a complex of
coagulation factors that functions in catalyzing prothrombin into
thrombin
• Fibrinogen: Fibrinogen is the major plasma coagulation factor
• Antithrombin: it is a small protein molecule that inactivates
several enzymes of the coagulation system. (Factors IIa, IXa, Xa).
 Stages of Blood Clotting

In general, blood clotting occurs in three stages:

• 1. Formation of prothrombin activator
• 2. Conversion of prothrombin into thrombin
• 3. Conversion of fibrinogen into fibrin.
 Anticoagulants
(Heparin, Warfarin, Rivaroxaban)
Anticoagulants are those substances which prevent coagulation
of blood.
Anticoagulants are of three types:
1. Anticoagulants used to prevent blood clotting inside the body,
i.e. in vivo (In the living organism). Eg , warfarin
2. Anticoagulants used to prevent clotting of blood that is
collected from the body, i.e. in vitro.
3. Anticoagulants used to prevent blood clotting both in vivo and
in vitro. Eg heparin
Anticoagulants and antiplatelet agents are medicines that
reduce blood clotting in an artery, a vein or the heart.
In vitro anticoagulants: those that remove calcium ions from the blood to prevent
coagulation, such as citrate, oxalate, fluoride, and ethylene diamine tetra acetic
acid (EDTA)
Stages of blood coagulation
 Heparin
• Heparin is a naturally produced anticoagulant in the body. It is
produced by mast cells and basophils.
• Mechanism of Action of Heparin: It prevents blood clotting by
its antithrombin activity. It directly suppresses the activity of
thrombin (Combines with antithrombin III (a protease inhibitor
present in circulation) and removes thrombin from circulation).
Heparin is enhancing the activity of the endogenous inhibitor,
antithrombin by 1000 x.
Mechanism of action of heparin
 Heparin Pharmacokinetics
• Absorption and Distribution: Because of its polarity and large
size, heparin is unable to cross membranes, including those of
the GI tract. Consequently, heparin cannot be absorbed if
given orally, and therefore must be given by injection (IV or
subQ). Since it cannot cross membranes, heparin does not
traverse the placenta and does not enter breast milk.
• Metabolism and Excretion: Heparin undergoes hepatic
metabolism and excreted through renal route.
• Under normal conditions, the half-life is short (about 1.5
hours). However, in patients with hepatic or renal disease, the
half-life is increased.
 Adverse Effects and Contraindications

• Hemorrhage: bruises, petechiae, hematomas

• Heparin-Induced Thrombocytopenia
Precautions: hemophilia, increased capillary
.
permeability, peptic ulcer disease

Contraindicated: Heparin is contraindicated

for patients with thrombocytopenia

activated partial thromboplastin time (aPTT). (normal

range is 30-40 seconds)
PT (prothrombin time) range is 11 to 14 seconds
 Heparin—Clinical Applications
• Prophylaxis and treatment of Venous
thrombosis (DVT)
• Pulmonary Embolism(PE)
• Peripheral arterial embolism
• Prevention of post-op DVT/PE
• Treatment of DIC??
• Prevention of clotting in surgery
• Anticoagulant in blood transfusions and dialysis
Disseminated intravascular coagulation (DIC) is a condition in which blood clots
form throughout the body blocking small blood vessels
 Protamine Sulfate for Heparin Overdose
• 1 unit of heparin means the amount of heparin that will
prevent 1 mL of sheep plasma from coagulating for 1 hour
• Antidote of heparin: Protamine sulfate
• Protamine sulfate is an antidote to severe heparin
overdose. Protamine is a small protein that has multiple
positively charged groups. These groups bond ionically
with the negative groups on heparin
• Dosage of protamine is based on the fact that 1 mg of
protamine will inactivate 100 units of heparin. Hence, for
each 100 units of heparin in the body, 1 mg of protamine
should be injected.
 Nursing Considerations

• The nurse obtains baseline vital signs and physical

assessment.
• He/she must obtain laboratory results of the complete
blood count, platelet count and activated partial
thromboplastin time (aPTT), and clotting time.
• Monitor signs of bleeding- hematuria, epistaxis,
ecchymosis, Hypotension and occult blood in stool
• Have available ANTIDOTE for heparin- PROTAMIME
SULFATE
• Instruct the client not to use any over the counter drug
without notifying the physician.
 Factor X inhibitor
Rivaroxaban 2007
• Rivaroxaban is an anticoagulant taken orally
• Indicated for prophylaxis of deep vein thrombosis (DVT), which
may lead to pulmonary embolism (PE) in patients undergoing
knee or hip replacement surgery
• MOA: Rivaroxaban inhibits both free Factor Xa and Factor Xa
bound in the prothrombinase complex
• Inhibition of Factor Xa interrupts the intrinsic and extrinsic
pathway of the blood coagulation cascade, inhibiting
both thrombin formation and development of thrombi.
 Factor X inhibitor
Rivaroxaban 2007
• Averse effects
– Thrombocytopenia
– Retroperitoneal hemorrhage
– Hypersensitivity
– Cerebral hemorrhage
Why new born babies are given Vitamin K?

Newborns are prone to vitamin K deficiency

because…
• 1.Vitamin K is not easily transported across the
placental barrier
• 2.Prothrombin synthesis in the liver is an immature
process in newborns, especially when premature.
• 3.The neonatal gut is sterile, lacking the bacteria
that is necessary in Vitamin K synthesis.
 Warfarin

• Warfarin is an anticoagulant used to prevent clots.

Vitamin K antagonists act only in vivo and have no
effect on clotting if added to blood in vitro.
• Role of vitamin k: The clotting factors II
(prothrombin) VII, IX and X are synthesized as
inactive precursors (zymogens) in the liver. Vitamin K
act as a Coenzyme for activation.
Warfarin
 Mechanism of action of warfarin

Warfarin inhibits the vitamin K-dependent synthesis of

clotting factors II, VII, IX and X. Warfarin acts as a substrate
for Vit k epoxide reductase and inhibits the conversion of
vitamin K epoxide to Vit. K hydroquinone
Side effects of warfarin
• Severe bleeding, including heavier than normal menstrual
bleeding.
• Hematuria
• Black or bloody stool.
• Blood in vomiting
• Blood in sputum.
 Pharmacokinetics
• Warfarin is readily absorbed following oral dosing.
Once in the blood, about 99% of warfarin binds to
albumin. Warfarin molecules that remain free
(unbound) can readily cross membranes, including
those of the placenta and milk-producing glands
• warfarin has a long half-life (1.5 to 2 days)
 Fibrinolytics

• Blood clot is defined as the mass of coagulated blood

which contains RBCs, WBCs and platelets entrapped
in fibrin meshwork.
• RBCs and WBCs are not necessary for clotting
process. However, when clot is formed, these cells
are trapped in it along with platelets. The trapped
RBCs are responsible for the red color of the clot.
• Fibrinolysis: Lysis of blood clot inside the blood
vessel is called fibrinolysis. It helps to remove the clot
from lumen of the blood vessel.
Fibrin clot
 Fibrinolysis
• Lysis of blood clot inside the blood vessel is called fibrinolysis.
It helps to remove the clot from lumen of the blood vessel.
This process requires a substance called plasmin or
fibrinolysin.
• Plasmin is formed from inactivated plasminogen.
• Plasminogen is synthesized in the liver.
• Plasminogen is converted into plasmin by tissue plasminogen
activator(tPA). It is a protein involved in the breakdown of
blood clots.
 Formation of Plasmin

• Plasmin is formed from inactivated glycoprotein

called plasminogen.
• Plasminogen is synthesized in liver
• Plasminogen is converted into plasmin by
plasminogen activator called urokinase plasminogen
activator (u-PA). It is derived from blood.
 Fibrinolytics or Thrombolytic drugs

• Alteplase
• Reteplase
• Anistreplase
• Streptokinase
• Urokinase
 Mechanism of action of fibrinolytics

• Plasmin is produced in the blood to break

down fibrin, the major constituent of blood thrombi,
thereby dissolving clots once they have fulfilled their
purpose of stopping bleeding.
• Fibrinolytics i.e. streptokinase activate
plasminogen to produce plasmin. And plasmin then
break down fibrin
 Side effects

• Besides risk of serious internal bleeding,

other possible risks include:
• Bruising or bleeding at the access site
• Damage to the blood vessel.
• Migration of the blood clot to another part of
vascular system.
 Antiplatelets (aspirin, clopidogrel, and
Prasugrel)
• Antiplatelets are a group of medicines that stop
blood cells (called platelets) from sticking together
and forming a blood clot.
 Basic steps
• Prothrombin activator --> Prothrombin -->
Thrombin --> Fibrinogen --> Fibrin
• Platelets activation: increase expression of
glycoprotein IIb/IIIa (GPIIb/IIIa, also known
as integrin).
• What increase the above?
Answer: Thromboxane A2, ADP (adenosine
diphosphate), and thrombin.
Platelet activation step's
 Adenosine diphosphate

• Under normal conditions, platelets circulate in the

blood freely and without interaction with one
another. ADP is stored in inside platelets and is
released upon platelet activation. ADP interacts with
a family of ADP receptors found on platelets (P2Y12)
which leads to platelet aggregation.
 What is thromboxane A2?

• Thromboxane A2 is a type of thromboxane that is

produced by activated platelets and has
prothrombotic properties
• It stimulates activation of new platelets as well as
increases platelet aggregation. This is achieved by
increasing expression of the glycoprotein
complex GPIIb/IIIa.
 What is thromboxane?

• Thromboxane is a member of the family

of lipids known as eicosanoids(lipids)
• Thromboxane-A synthase, an enzyme found
in platelets, converts the arachidonic acid to
thromboxane-A2 which activate aggregation of
platelets by increasing the expression of the
glycoprotein complex GPIIb/IIIa.
 How do Clopidogrel and Aspirin act as
antiplatelete?
• Clopidogrel acts by inhibiting the ADP receptor
on platelet cell membranes. The drug specifically and
irreversibly inhibits the P2Y12 subtype of ADP
receptor, which is important in activation of platelets
and cross-linking by the protein fibrin.
• Aspirin in lower doses(75-150 mg) exert antiplatelet
effect by prevent the synthesis of thromboxane A2 by
inhibiting Thromboxane-A synthase.
Glycoprotein IIb/IIIa Receptor Antagonists

• The GP IIb/IIIa antagonists cause reversible blockade

of platelet GP IIb/IIIa receptors, and thereby inhibit
the final step in aggregation
• As a result, these drugs can prevent aggregation
stimulated by all factors, including collagen, TXA2,
ADP, thrombin, and platelet activation factor.
• DRUGS: Abciximab, Tirofiban (aggrastat),
 Side Effects

• Headaches or dizziness.
• Nausea.
• Diarrhea or constipation.
• Indigestion (dyspepsia)
• Stomach ache or abdominal pain.
• Nose bleeds.
• Increased bleeding
Tranexamic acid
 Mechanism

• Tranexamic acid is an antifibrinolytic that

competitively inhibits the activation of
plasminogen to plasmin
 Tranexamic acid indications

Tranexamic acid: it is used to treat or prevent

excessive blood loss from
• major trauma,
• post partum bleeding,
• surgery,
• tooth removal,
• nose bleeds (epistaxis)
 References
• Karch, A. M., & Karch. (2011). Focus on nursing pharmacology.
Wolters Kluwer Health/Lippincott Williams & Wilkins. [Link]
• Katzung, B. G. (2017). Basic and clinical pharmacology.
McGraw-Hill Education.
• Lehne, R. A., Moore, L. A., Crosby, L. J., & Hamilton, D. B.
(2004). Pharmacology for nursing care.
• Smeltzer, S. C., & Bare, B. G. (1992). Brunner & Suddarth’s
textbook of medical-surgical nursing. Philadelphia: JB
Lippincott