OXYGENATION:

HEMATOLOGIC
PATHOPHYSIOLOGY
ALLEN OCTAVIANO CUDIAMAT

OUTLINE

ANEMIAS

POLYCYTHEMIA

ALTERATIONS OF PLATELET AND

COAGULATION

anemia

Normal hematologic parameters

anemia

reduction in the number of erythrocytes, in the

concentration of hemoglobin and/or in the hematocrit as
long as the total blood volume is normal.

classification according to:

cell volume (mean corpuscular volume, MCV):

microcytic,

normocytic, or macrocytic

ratio of Hb concentration/erythrocyte count (mean

corpuscular hemoglobin, MCH):
hypochromic,

normochromic, or hyperchromic.

Pathogenetic division of the anemias reflects the

individual steps of erythropoiesis as well as the life-span
of the erythrocytes circulating in blood (hemolytic
anemia).

acute or chronic blood loss can also lead to anemia.

anemia
Causes of Disorders of erythropoiesis:

1) lack or absence of differentiation of pluripotent, hemopoietic

stem cells (aplastic anemia in panmyelopathy or acute myeloid
leukemia);

2) transient (viral infection) or chronic reduction of only the

erythrocytic precursor cells (isolated aplastic anemia) due to
autoantibodies against erythropoietin or against membrane
proteins of the precursor cells;

3) erythropoietin deficiency in renal failure (renal anemia);

4) chronic inflammation or tumors that can activate, among

others, erythropoiesis- inhibiting interleukins (secondary
anemia);

5) abnormal cell differentiation (ineffective erythropoiesis),

which in addition to gene defectsmay mainly be due to a
deficiency in folic acid or vitamin B12 (megaloblastic anemia);

6) abnormal Hb synthesis (microcytic hypochromic anemia).

anemia

anemia

manifestations
COMMON:

Weakness, fatigue, general malaise, AND pallor of the

skin and mucous membranes (sclera, oral mucosa).

increased cardiac workload: tachycardia, palpitations,

dyspnea, dizziness, orthopnea, and exertional dyspnea.

Heart failure: enlarged heart (cardiomegaly) and liver

(hepatomegaly) and peripheral edema.

IDA

tongue may be smooth and red

may crave ice, starch, or dirt (known as pica); nails

may be brittle, ridged, and concave.

manifestations
PERNICIOUS

peripheral numbness and paresthesias, ataxia, poor

coordination, and confusion.

OTHERS:

Jaundice - megaloblastic anemia or hemolytic anemia.

Tongue is beefy red and sore - megaloblastic anemia

angular cheilosis - corners of the mouth may be

ulcerated IDA, megaloblastic

polycythemia

POLYCYTHEMIA
increased

volume of RBCs.
hematocrit is elevated (to more
than 55% in males, more than
50% in females).
either primary (POLYCYTHEMIA
VERA) or secondary.

POLYCYTHEMIA VERA

proliferative disorder in which the myeloid stem cells seem to

have escaped normal control mechanisms.

The bone marrow is hypercellular, and the RBC, WBC, and

platelet counts in the peripheral blood are elevated.

RBC elevation is predominant; the hematocrit can exceed 60%.

This phase can last for an extended period (10 years or longer).

The spleen resumes its embryonic function of hematopoiesis and

enlarges.

Over time, the bone marrow may become fibrotic, with a

resultant inability to produce as many cells(burnt out or spent
phase).

The disease evolves into myeloid metaplasia with myelofibrosis

or AML in a significant proportion of patients; this form of AML is
usually refractory to standard treatments

The median survival time exceeds 15 years

POLYCYTHEMIA VERA
MANIFESTATIONS:

ruddy complexion and splenomegaly (enlarged

spleen).

increased blood volume: headache, dizziness,

tinnitus, fatigue, paresthesias, and blurred vision

increased blood viscosity: angina, claudication,

dyspnea, and thrombophlebitis

generalized pruritus - caused by histamine release

due to the increased number of basophils.

Erythromelalgia - a burning sensation in the

fingers and toes and is only partially relieved by
cooling.

POLYCYTHEMIA VERA

COMPLICATION:
CVA (brain
heart

attack, stroke)

attack (MI)

thrombotic

complications are the most

frequent cause of death.

Bleeding

- platelets (often very large) are

somewhat dysfunctional.
nosebleeds,

bleeding.

ulcers, and frank gastrointestinal

SECONDARY POLYCYTHEMIA

excessive production of erythropoietin.

CAUSES:

reduced amount of oxygen (hypoxic stimulus):

cigarette smoking, chronic obstructive pulmonary

disease, or cyanotic heart disease

nonpathologic conditions such as high altitude.

certain hemoglobinopathies in which the

hemoglobin has an abnormally high affinity for
oxygen (eg, hemoglobin Chesapeake).

Neoplasms (eg, renal cell carcinoma) that

stimulate erythropoietin production.

alterations of platelet and

coagulation

Platelet and coagulation disorders

thrombocytopenia

Low platelet count

MANIFESTATIONS:

Bleeding and petechiae usually do not occur with platelet

counts greater than 50,000/mm3

excessive bleeding can follow surgery or other trauma.

platelet count below 20,000/mm3, petechiae can appear, along

with nose and gingival bleeding, excessive menstrual bleeding,
and excessive bleeding after surgery or dental extractions.

platelet count is less than 5000/mm3: spontaneous, potentially

fatal central nervous system or gastrointestinal hemorrhage can
occur.

If the platelets are dysfunctional due to disease (eg, MDS) or

medications (eg, aspirin), the risk of bleeding may be much
greater even when the actual platelet count is not significantly
reduced.

idiopathic thrombocytopenic
purpura (ITP)

precise cause: unknown

viral infections sometimes precede ITP in children.

medications such as sulfa drugs can induce ITP.

Systemic lupus erythematosus (SLE) or pregnancy, can

also induce ITP.

Anti-platelet autoantibodies that bind to the

patients platelets are found in the blood of patients
with ITP. When the platelets are bound by the
antibodies, the RES or tissue macrophage system
ingests the platelets, destroying them. The body
attempts to compensate for this destruction by
increasing platelet production within the marrow.

idiopathic thrombocytopenic
purpura (ITP)
MANIFESTATIONS

are easy bruising, heavy menses, and petechiae on the extremities

or trunk.

DRY PURPURA:

simple bruising or petechiae

tend to have fewer complications

WET PURPURA:

bleeding from mucosal surfaces, such as the gastrointestinal tract

(including the mouth) and pulmonary system (eg, hemoptysis)

greater risk for intracranial bleeding

Despite low platelet counts, the platelets are young and very
functional. They adhere to endothelial surfaces and to one another,
so spontaneous bleeding does not always occur.

HEMOPHILIA

Hemophilia A is caused by a genetic defect that results in deficient

or defective factor VIII;

Hemophilia B (Christmas disease) stems from a genetic defect that

causes deficient or defective factor IX.

Hemophilia is a relatively rare disease; hemophilia A is three times

more common than hemophilia B.

Both types of hemophilia are inherited as X-linked traits, so almost

all affected people are males; females can be carriers but are
almost always asymptomatic.

The disease is recognized in early childhood, usually in the toddler

age group.

mild hemophilia may not be diagnosed until they experience severe

trauma (eg, a high-school football injury) or surgery.

Hemophilia occurs in all ethnic groups.

HEMOPHILIA

Hemorrhages into various parts of the body.

The frequency and severity of the bleeding depend

on the degree of factor deficiency as well as the
intensity of the precipitating trauma.

JOINT BLEEDING 70% of patients

chronic pain or ankylosis (fixation) of the joint

Hematomas

Intracranial bleeds

Disseminated intravascular
coagulation (DIC)

normal hemostatic mechanisms are

altered so that a massive amount of tiny
clots forms in the microcirculation.

Initially, the coagulation time is normal.

However, as the platelets and clotting

factors are consumed to form the
microthrombi, coagulation fails.

Thus, the paradoxical result of excessive

clotting is bleeding.

DIC

DIC

PATHOPHYSIOLOGY

DIC
MANIFESTATIONS:

bleed from mucous membranes,

venipuncture sites, and the
gastrointestinal and urinary tracts.

range from minimal occult internal

bleeding to profuse hemorrhage

organ dysfunction, such as renal failure

and pulmonary and multifocal central
nervous system infarctions as a result of
microthromboses, macrothromboses, or
hemorrhages.

DIC

Recognizing
Thrombosis and
Bleeding in
Disseminated
Intravascular
Coagulation

DIC
Recognizing
Thrombosis and
Bleeding in
Disseminated
Intravascular
Coagulation

DIC
COMPLICATIONS:

Renal failure

Gangrene

Pulmonary embolism or hemorrhage

Altered level of consciousness

Acute respiratory distress syndrome

Stroke

danke