Blood Disorders

1. Hematologic Disorders

2. GENERAL OVERVIEW
• Blood, the body fluid circulating through the heart, arteries, capillaries,
and veins, consists of plasma and cellular components.
• The average male adult has about 5.5 L of blood &
• The average female 4.5 L.
• Plasma, the fluid portion, accounts for 55% of the blood volume and is
composed of 92% water, 7% protein, and 1% inorganic salts; non protein
organic substances such as urea; dissolved gases; hormones; and
enzymes.
• Plasma proteins include albumin, fibrinogen, and globulins.
• Cellular components include erythrocytes (red blood cells [RBCs]),
leukocytes and lymphocytes (white blood cells [WBCs]), and platelets.
• These cells are derived from pluripotent stem cells in the bone marrow, a
process known as hematopoiesis

3. • Erythrocytes (RBCs)
• Leukocytes and lymphocytes (white blood
cells [WBCs]),
• Platelets (Thrombocytes)

4. ANEMIAS

9. ANEMIAS
• Anemia is the lack of sufficient circulating hemoglobin to deliver
oxygen to tissues.
Causes : Commonly associated with other diseases and disorders (eg,
renal disease, cancer, Crohn's disease, alcoholism).
• Anemia may be caused by inadequate production of RBCs,
abnormal hemolysis and sequestration of RBCs, or blood loss.
Types of anemia
• Iron deficiency anemia,
• pernicious anemia,
• folic acid deficiency, and
• aplastic anemia are the anemias most commonly seen in adults.

20. IRON DEFICIENCY ANEMIA (MICROCYTIC,
HYPOCHROMIC)
• Iron deficiency anemia is a condition in which
the total body iron content is decreased below
a normal level, affecting hemoglobin
synthesis. RBCs appear pale and are small.

21. CAUSES
• The most common cause is chronic blood loss
(GI bleeding, excessive menstrual bleeding,
hookworm infestation), but anemia may also
be caused by insufficient intake of iron (weight
loss, inadequate diet), iron malabsorption
(small bowel disease, gastroenterostomy), or
increased requirements (pregnancy, periods of
rapid growth).

22. Clinical Manifestations
• Headache, dizziness, fatigue, tinnitus
• Palpitations, dyspnea on exertion, pallor of
skin and mucous membranes
• Smooth, sore tongue; cheilosis (lesions at
corners of mouth)
• Koilonychia (spoon-shaped fingernails)
• Pica (craving to eat unusual substances)

23. Diagnostic Evaluation
• CBC and iron profile decreased hemoglobin,
hematocrit, serum iron, and ferritin; elevated
red cell distribution width and normal or
elevated total iron-binding capacity.
• Determination of source of chronic blood loss
may include sigmoidoscopy, colonoscopy,
upper and lower GI studies, stool and urine for
occult blood examination.

24. Management
• Correction of chronic blood loss.
• Oral or parenteral iron therapy.
– Oral ferrous sulfate preferred and least expensive;
treatment continues until hemoglobin level is
normalized and iron stores replaced (up to 6 months).
– Parenteral therapy may rarely be used when patient
cannot tolerate or is noncompliant with oral therapy.
May use iron dextran (Imferon) or iron sorbitex
(Jectofer).

25. MEGALOBLASTIC ANEMIA:
PERNICIOUS
• A megaloblast is a large, nucleated
erythrocyte with delayed and abnormal
nuclear maturation. Pernicious anemia is a
type of megaloblastic anemia associated with
vitamin B2 deficiency.

26. CAUSES
• Normal gastric mucosa secretes a substance
called intrinsic factor, necessary for absorption of
vitamin B12 in ileum. If a defect exists in gastric
mucosa, or after gastrectomy or small bowel
disease, intrinsic factor may not be secreted and
orally ingested B12 not absorbed.
• Some drugs interfere with B12 absorption, notably
ascorbic acid, cholestyramine, colchicine,
neomycin, cimetidine, and hormonal
contraceptives.

27. Clinical Manifestations
• pallor, fatigue, dyspnea on exertion, palpitations. May
be angina pectoris and heart failure in the elderly or
those predisposed to heart disease.
• Of underlying GI dysfunction, sore mouth, glossitis,
anorexia, nausea, vomiting, loss of weight, indigestion,
epigastric discomfort, recurring Diarrhea or
constipation.
• Of neuropathy (occurs in high percentage of untreated
patients), paresthesia that involves hands and feet, gait
disturbance, bladder and bowel dysfunction,
psychiatric symptoms caused by cerebral dysfunction.

28. Diagnostic Evaluation
• CBC and blood smear decreased haemoglobin and
hematocrit marked variation in size and shape of RBCs
with a variable number of unusually large cells
• Folic acid (normal) and B12 levels (decreased).
• Gastric analysis volume and acidity of gastric juice
diminished.
• Schilling test for absorption of vitamin B12 uses small
amount of radioactive B12 orally and 24-hour urine
collection to measure uptake—decreased.

29. Management
• Parenteral replacement with
hydroxocobalamin or cyanocobalamin (B12) is
necessary by I.M. injection from health care
provider, generally every month.

30. MEGALOBLASTIC ANEMIA: FOLIC ACID
DEFICIENCY
• Chronic megaloblastic anemia caused by folic
acid (folate) deficiency.

31. CAUSES
• Dietary deficiency, malnutrition, marginal diets,
excessive cooking of foods; commonly associated with
alcoholism.
• Impaired absorption in jejunum (eg, with small bowel
disease).
• Increased requirements (eg, with chronic hemolytic
anemia, exfoliative dermatitis, pregnancy).
• Impaired utilization from folic acid antagonists
(methotrexate) and other drugs (phenytoin, broad
spectrum antibiotics, sulfamethoxazole, alcohol,
hormonal contraceptives).

32. Clinical Manifestations
• fatigue, weakness, pallor, dizziness, headache,
tachycardia.
• Of folic acid deficiency: sore tongue, cracked
lips.

33. Diagnostic Evaluation
• Vitamin B12 and folic acid level folic acid will be
decreased.
• CBC will show decreased RBC, haemoglobin, and
hematocrit with increased mean corpuscular volume
and mean corpuscular haemoglobin concentration.
Management
• Oral folic acid replacement on daily basis.

34. APLASTIC ANEMIA
• Aplastic anaemia is a disorder characterized by
bone marrow hypoplasia or aplasia resulting
in pancytopenia (insufficient numbers of RBCs,
WBCs, and platelets).

35. CAUSES
• Destruction of hematopoietic stem cells is
thought to be through an immune-mediated
mechanism.
• May be idiopathic or caused by exposure to
chemical toxins; ionizing radiation; viral
infections, particularly hepatitis; certain drugs
(eg, chloramphenicol).
• May be congenital (Fanconi's anemia).
• Clinical course is variable and dependent on
degree of bone marrow failure; severe aplastic
anemia is almost always fatal if untreated.

36. Clinical Manifestations
• Pallor, weakness, fatigue, exertional dyspnea,
palpitations.
• From infections associated with neutropenia:
fever, headache, malaise; adventitious breath
sounds; abdominal pain, diarrhea; erythema,
pain, exudate at wounds or sites of invasive
procedures.
• From thrombocytopenia: bleeding from gums,
nose, GI or GU tracts; purpura, petechiae,
ecchymoses.

37. Diagnostic Evaluation
• CBC and peripheral blood smear show decreased RBC, WBC, platelets
(pancytopenia).
• Bone marrow aspiration and biopsy: bone marrow is hypocellular or
empty with greatly reduced or absent hematopoiesis.
Management
• Removal of causative agent or toxin.
• Allogeneic bone marrow transplantation (BMT) treatment of choice for
patient with severe aplastic anemia.
• Immunosuppressive treatment with corticosteroids, cyclosporine,
cyclophosphamide, antithymocyte globulin or antilymphocyte globulin as
single treatments or in combinations.
• Androgens (oxymetholone or testosterone enanthate) may stimulate bone
marrow regeneration; significant toxicity encountered. They may be used
when other treatments have failed.
• Supportive treatment includes platelet and RBC transfusions, antibiotics,
and antifungal.

41. MYELOPROLIFERATIVE DISORDERS
Myeloproliferative disorders are disorders of the bone marrow
that result from abnormal proliferation of cells from the
myeloid line of the hematopoietic system. They include
polycythemia vera, acute lymphocytic and acute myelogenous
leukemia, and chronic myelogenous leukemia.

42. POLYCYTHEMIA VERA
Polycythemia vera is a chronic
myeloproliferative disorder that involves all
bone marrow elements, resulting in an
increase in RBC mass and hemoglobin.
CAUSE : UNKOWN

43. PATHOPHYSIOLOGY
• Hyperplasia of all bone marrow elements results
in:
– Overproduction of all three blood cell lines, most
prominently RBCs.
– Increased red cell mass.
– Increased blood volume and viscosity.
– Decreased marrow iron reserve.
– Splenomegaly.
• Increased mass of blood cells increases viscosity
and leads to engorgement of blood vessels and
possible thrombosis.

44. Clinical Manifestations
• Result from increased blood volume and viscosity.
• Reddish purple skin and mucosa, pruritus (especially
after bathing).
• Splenomegaly, hepatomegaly.
• Epigastric discomfort, abdominal discomfort.
• Painful fingers and toes from arterial and venous
insufficiency, paresthesia.
• Headache, fullness in head, dizziness, visual
abnormalities, Weakness, fatigue, night sweats,
bleeding tendency.
• Hyperuricemia from increased formation and
destruction of erythrocytes and leukocytes and
increased metabolism of nucleic acids.
• Itching related to histamine release from basophils.

45. Diagnostic Evaluation
• CBC elevated RBC and hemoglobin and hematocrit (> 60%);
elevated platelets.
• Bone marrow aspirate and biopsy hyperplasia.
• Elevated uric acid.
Management
• Of hyperviscosity: phlebotomy (withdrawal of blood) at intervals
determined by CBC results to reduce RBC mass; generally, 250 to
500 mL removed at a time.
• Of marrow hyperplasia: myelosuppressive therapy, generally using
hydroxyurea (Hydrea) or I.V. radioactive phosphorus; biologic
response modifier, ie, alpha-interferon.
• Of hyperuricemia: allopurinol (Zyloprim).
• Of pruritus: antihistamines (cimetidine [Tagamet]

46. LEUKEMIA
ACUTE LYMPHOCYTIC AND ACUTE MYELOGENOUS LEUKEMIA
IT Is malignant disorders of the blood and bone marrow that result in an
accumulation of dysfunctional, immature cells that are caused by loss of
regulation of cell division. They are classified as acute or chronic based on
the development rate of symptoms, and further classified by the
predominant cell type.
Acute leukemias affect immature cells and are characterized by rapid
progression of symptoms. When lymphocytes are the predominant
malignant cell, the disorder IS ACUTE LYMPHOCYTIC LEUKEMIA (ALL);
when monocytes or granulocytes are predominant, it is acute
myelogenous leukemia (AML), sometimes called ACUTE
NONLYMPHOCYTIC LEUKEMIA.

47. CAUSES
• The development of leukemia has been
associated with:
– Exposure to ionizing radiation.
– Exposure to certain chemicals and toxins (eg,
benzene, alkylating agents).
– Human T-cell leukemia—lymphoma virus (HTLV-
1 and HTLV-2) in certain areas of the world,
including the Caribbean and southern Japan.
– Familial susceptibility

48. Clinical Manifestations
• Common symptoms include pallor, fatigue,
weakness, fever, weight loss, abnormal
bleeding and bruising, lymphadenopathy (in
ALL), and recurrent infections (in ALL).
• Other presenting symptoms may include bone
and joint pain, headache, splenomegaly,
hepatomegaly, neurologic dysfunction.

49. Diagnostic Evaluation
• CBC and blood smear—peripheral WBC count varies
widely from 1,000 to 100,000/mm3 .
numbers of abnormal immature (blast) cells; anemia may
be profound; platelet count may be abnormal and
coagulopathies may exist.
• Bone marrow aspiration and biopsy—cells also studied for
chromosomal abnormalities (cytogenetics) and
immunologic markers to classify type of leukemia further.
• Lymph node biopsy—to detect spread.
• Lumbar puncture and examination of cerebrospinal fluid for
leukemic cells (especially in ALL).

50. Management
• To eradicate leukemic cells and allow restoration of normal
hematopoiesis.
– High-dose chemotherapy given as an induction course to obtain
a remission (disappearance of abnormal cells in bone marrow
and blood) and then in cycles as consolidation or maintenance
therapy to prevent recurrence of disease
– Leukapheresis (or exchange transfusion in infants) may be used
when abnormally high numbers of white cells are present to
reduce the risk of leukostasis and tumor burden before
chemotherapy.
– Radiation, particularly of central nervous system (CNS) in ALL.
– Autologous or allogeneic bone marrow or stem cell
transplantation.

51. CHRONIC MYELOGENOUS LEUKEMIA
• Chronic myelogenous leukemia (CML) (ie,
involving more mature cells than acute
leukemia) is characterized by proliferation of
myeloid cell lines, including granulocytes,
monocytes, platelets, and occasionally RBCs.

52. CAUSES
• Specific etiology unknown, associated with exposure to
ionizing radiation and family history of leukemia.
Results from malignant transformation of pluripotent
hematopoietic stem cell.
• First cancer associated with chromosomal abnormality
(the Philadelphia [Ph] chromosome), present in more
than 90% of patients.
Clinical Manifestations
• Insidious onset, may be discovered during routine
physical examination.
• Common symptoms include fatigue, pallor, activity
intolerance, fever, weight loss, night sweats, abdominal
fullness (splenomegaly).

53. Diagnostic Evaluation
• CBC and blood smear: large numbers of granulocytes (usually more
than 100,000/mm3), platelets may be decreased.
• Bone marrow aspiration and biopsy: hypercellular, usually
demonstrates Philadelphia (Ph1) chromosome.
Management
• Chronic Phase
• A protein-tyrosine kinase inhibitor, it works by inhibiting
proliferation of abnormal cells and inducing cell death (apoptosis) in
abnormal cells. Adverse effects include edema, GI irritation,
hematologic toxicity and, rarely, hepatotoxicity.
• For patients who cannot tolerate imatinib mesylate, alpha
interferon frequently eliminates the Ph1 chromosome and blasts.
Adverse effects (most commonly fatigue and fevers) may be severe.
• Allogeneic (related or unrelated donor) BMT.
• Palliative treatment, controlling symptoms, includes chemotherapy
with such agents as busulfan (Myleran) or hydroxyurea (Hydrea);
irradiation; splenectomy.

54. LYMPHOPROLIFERATIVE
DISORDERS
Lymphoproliferative disorders result from proliferation
of cells from the lymphoid line of the hematopoietic
system. They include chronic lymphocytic leukemia,
Hodgkin's lymphoma, non-Hodgkin's lymphomas, and
multiple myeloma.

55. CHRONIC LYMPHOCYTIC LEUKEMIA
• Chronic lymphocytic leukemia (CLL) (ie, involving
more mature cells than acute leukemia) is
characterized by proliferation of morphologically
normal but functionally inert lymphocytes.
• Classified according to cell origin, it includes B cell
(accounts for 95% of cases), T cell,
lymphosarcoma, and prolymphocytic leukemia.

56. Clinical Manifestations
• Insidious onset, may be discovered during routine physical
examination.
• Early symptoms may include history of frequent skin or respiratory
infections, symmetrical lymphadenopathy, mild splenomegaly.
• Symptoms of more advanced disease include pallor, fatigue, activity
intolerance, easy bruising, skin lesions, bone tenderness, abdominal
discomfort.
Diagnostic Evaluation
• CBC and blood smear: large numbers of lymphocytes (10,000 to
150,000/mm3); may also be anemia, thrombocytopenia,
hypogammaglobulinemia.
• Bone marrow aspirate and biopsy: lymphocytic infiltration of bone
marrow.
• Lymph node biopsy to detect spread.

57. Management
• Symptom Control and Treatments
• Lymphocyte proliferation can be suppressed with chlorambucil (Leukeran),
cyclophosphamide (Cytoxan), and prednisone (Orasone).
• B cell CLL may be treated with fludarabine (Fludara).
• Monoclonal antibodies such as alemtuzumab (Campath) and rituximab
(Rituxan) may be used.
• Hairy cell leukemia, a distinctive type of B cell leukemia with hairlike
projections of cytoplasm from lymphocytes, may be successfully treated
with cladribine (Leustatin), pentostatin (Nipent), or alpha interferon.
• Splenic irradiation or splenectomy for painful splenomegaly or platelet
sequestration, hemolytic anemia.
• Bone marrow transplant and combinations of alpha interferon and
interleukin-2 are also used to treat CLL.
Supportive Care
• Transfusion therapy to replace platelets and RBCs.
• Antibiotics, antivirals, and antifungals as needed to control infections.
• I.V. immunoglobulins or gamma globulin to treat hypogammaglobulinemia.

58. HODGKIN'S LYMPHOMA
• Lymphomas are malignant disorders of the
reticuloendothelial system that result in an
accumulation of dysfunctional, immature lymphoid-
derived cells.
• They are classified according to the predominant cell
type and by the degree of malignant cell maturity (eg,
well differentiated, poorly differentiated, or
undifferentiated).
• Hodgkin's lymphoma originates in the lymphoid system
and involves predominantly lymph nodes.

59. • Etiology is unknown.
• Characterized by appearance of Reed-Sternberg•
multinucleated giant cell in tumor. Generally spreads
via lymphatic channels, involving lymph nodes, spleen,
and ultimately extralymphatic sites.
• May also spread via bloodstream to such sites as GI
tract, bone marrow, skin, upper air passages, and other
organs.
• Incidence demonstrates two peaks, between ages 20
and 40 and after age 60. Risk is increased in males,

60. Clinical Manifestations
• Common symptoms include painless enlargement of lymph nodes
(generally unilateral), fever, chills, night sweats, weight loss, pruritus.
• Various symptoms may occur with pulmonary involvement, superior vena
cava obstruction, hepatic or bone involvement.
Diagnostic Evaluation
• Tests are used to determine extent of disease involvement before
treatment and followed at regular intervals to assess response to
treatment.
• CBC determines abnormal cells.
• Lymph node biopsy determines type of lymphoma.
• Bilateral bone marrow aspirate and biopsy determine whether bone
marrow is involved.
• Radiographic tests (eg, X-rays, computed tomography [CT] scan, magnetic
resonance imaging [MRI]) to detect deep nodal involvement.
• Gallium-67 scan detects areas of active disease and may be used to
determine aggressiveness of disease.
• Liver function tests, scan to determine hepatic involvement; liver biopsy
may be indicated if results abnormal.
• Lymphangiogram to detect size and location of deep nodes involved,
including abdominal nodes, which may not be readily seen via CT scan

61. Management
• Choice of treatment depends on extent of disease, histopathologic
findings, and prognostic indicators. Hodgkin's lymphoma is more readily
cured than other lymphomas, with a 5-year survival of 80%. More than
one treatment strategy is available, and combinations of radiation and
chemotherapy are commonly used. Hodgkin's lymphoma arising in
presence of HIV requires specialized treatment.
• Radiation therapy
– Treatment of choice for localized disease.
– Areas of body where lymph node chains are located can generally tolerate
high radiation doses.
– Vital organs are protected with lead shielding during radiation treatments.
• Chemotherapy
– Initial treatment commonly with ABVD regimen of doxorubicin (Adriamycin),
bleomycin (Blenoxane), vinblastine (Velban), and dacarbazine (DTIC) or MOPP
regimen of nitrogen mustard (Mustargen), vincristine (Oncovin), procarbazine
(Matulane), and prednisone.
– Three or four drugs may be given in intermittent or cyclical courses with
periods off treatment to allow recovery from toxicities.
• Autologous or allogeneic bone marrow or stem cell transplantation

62. NON-HODGKIN'S LYMPHOMAS
• Non-Hodgkin's lymphomas are a group of malignancies
of lymphoid tissue arising from T or B lymphocytes or
their precursors; include both indolent and aggressive
forms.
Causes :
• Association with defective or altered immune system;
and with some viruses (eg, HTLV-1 and Epstein-Barr).
Other risk factors include male gender, white ethnicity,
history of Helicobacter gastritis, history of Hodgkin's
lymphoma, history of radiation therapy, diet high in
meats and fat, exposure to certain pesticides

63. Clinical Manifestations
• Common symptoms include painless enlargement of lymph nodes
(generally unilateral), fever, chills, night sweats, weight loss,
unexplained pain in chest, abdomen, or bones. Unlike Hodgkin's
lymphoma, is more likely to be advanced disease at presentation.
• Various symptoms may occur with pulmonary involvement,
superior vena cava obstruction, hepatic or bone involvement.
Diagnostic Evaluation
• Lymph node biopsy to detect type.
• CBC, bone marrow aspirate and biopsy to detect bone marrow
involvement.
• X-rays, CT scan, positron-emission tomography scan, Gallium scan,
and MRI to detect deep nodal involvement.
• Liver function tests, liver scan to detect liver involvement.
• Lumbar puncture to detect CNS involvement.

64. Management
• Radiation therapy generally palliative, not curative.
• Chemotherapy: various regimens available, including CHOP regimen
of cyclophosphamide (Cytoxan), doxorubicin (Adriamycin),
vincristine (Oncovin), and prednisone (Orasone) or BACOP regimen
of bleomycin (Blenoxane), doxorubicin (Adriamycin),
cyclophosphamide (Cytoxan), vincristine (Oncovin), and prednisone.
• Monoclonal antibody therapy: rituximab (Rituxan), Yttrium-90-
labeled ibritumomab tiuxetan (Zevalin), generally given with
combination chemotherapy.
• Autologous or allogeneic bone marrow or stem cell transplantation.

65. PLATELET DISORDER

66. MULTIPLE MYELOMA
• Multiple myeloma is a malignant disorder of plasma cells.
Pathophysiology and Etiology
• Etiology unknown; genetic and environmental factors, such as chronic
exposure to low levels of ionizing radiation, may play a part.
• Characterized by proliferation of neoplastic plasma cells derived from one
B lymphocyte (clone) and producing a homogeneous immunoglobulin
without any apparent antigenic stimulation.
• Plasma cells produce osteoclast-activating factor leading to extensive
bone loss, severe pain, and pathologic fractures.
• Abnormal immunoglobulin affects renal function, platelet function,
resistance to infection, and may cause hyperviscosity of blood.
• Generally affects older people (median age at diagnosis is 68) and is more
common among black men and women.

67. Clinical Manifestations
• Constant, usually severe bone pain caused by bone lesions and
pathologic fractures; sites commonly affected include thoracic and
lumbar vertebrae, ribs, skull, pelvis, and proximal long bones.
• Fatigue and weakness related to anemia caused by crowding of
marrow by plasma cells.
• Proteinuria and renal insufficiency.
• Electrolyte disturbances, including hypercalcemia (bone
destruction), hyperuricemia (cell death, renal insufficiency).
Diagnostic Evaluation
• Bone marrow aspiration and biopsy demonstrate increased number
and abnormal form of plasma cells.
• CBC and blood smear changes reflect anemia.
• Urine and serum analysis for presence and quantity of abnormal
immunoglobulin.
• Skeletal X-rays osteolytic bone lesions.

68. Management
• Chemotherapy, including oral melphalan (Alkeran) or cyclophosphamide
(Cytoxan), high-dose corticosteroids alone or in combination with
chemotherapy.
• Thalidomide (Thalomid), an antiangiogenesis agent, with or without
chemotherapy or high-dose corticosteroids.
• Alpha interferon as maintenance therapy.
• Bortezomib (Velcade), a proteasome inhibitor, for treatment of relapse.
• Autologous or allogeneic bone marrow or peripheral blood stem cell
transplant in selected cases (usually younger than age 50 with no renal
failure, few bone lesions, and good organ function).
• Supportive care options:
– Plasmapheresis to treat hyperviscosity or bleeding.
– Radiation therapy for bone lesions.
– Biphosphanates (eg, pamidronate [Aredia]), potent inhibitors of bone
resorption, to treat hypercalcemia and alleviate bone pain.
– Allopurinol (Zyloprim) and fluids to treat hyperuricemia.
– Hemodialysis to manage renal failure.
– Surgical stabilization and fixation of fractures.

69. BLEEDING DISORDERS
Bleeding disorders may be congenital or acquired and
may be caused by dysfunction in any phase of
hemostasis (clot formation and dissolution). Bleeding
disorders seen in adults include thrombocytopenia,
idiopathic thrombocytopenic purpura (ITP), DIC, and
von Willebrand's disease.

70. THROMBOCYTOPENIA
• Thrombocytopenia is decreased platelet count (less than
100,000/mm3), the most common cause of bleeding disorders.
Pathophysiology and Etiology
• Decreased platelet production nfiltrative diseases of bone marrow,
leukemia, aplastic anemia, myelofibrosis, myelosuppressive
therapy, radiation therapy; may include inherited disorders, such as
Fanconi's anemia and Wiskott-Aldrich syndrome.
• Increased platelet destruction—infection, drug-induced (eg,
heparin), ITP, DIC.
• Abnormal distribution or sequestration in spleen.
• Dilutional thrombocytopenia after hemorrhage, RBC transfusions.

71. Clinical Manifestations
• Usually asymptomatic.
• When platelet count drops below 20,000/mm3:
– Petechiae occur spontaneously
– Ecchymoses occur at sites of minor trauma (venipuncture, pressure)
– Bleeding may occur from mucosal surfaces, nose, GI and GU tracts,
respiratory system, and within CNS
– Menorrhagia is common.
• Excessive bleeding may occur after procedures (dental extractions,
minor surgery, biopsies).
• Thrombotic complications (arterial and venous) and areas of skin
necrosis are associated with heparin-induced thrombocytopenia.

72. Diagnostic Evaluation
• CBC with platelet count decreased hemoglobin, hematocrit,
platelets.
• Bleeding time, prothrombin time (PT), partial thromboplastin time
(PTT) prolonged.
• Platelet aggregation test for heparin-dependent platelet antibodies
positive.
Management
• Platelet transfusions.
• Steroids or I.V. immunoglobulins may be helpful in selected
patients.
• Heparin-induced thrombocytopenia: discontinue heparin, use
alternate anticoagulant therapy due to high risk of thromboses
(direct thrombin inhibitors, such as argatroban or hirudin), avoid
platelet transfusions.

73. AUTOIMMUNE (IDIOPATHIC)
THROMBOCYTOPENIC PURPURA
• Autoimmune thrombocytopenic purpura, or idiopathic immune
thrombocytopenic purpura, is an acute or chronic bleeding disorder that
results from immune destruction of platelets by antiplatelet antibodies.
Pathophysiology and Etiology
• Autoantibodies of both immunoglobulin (Ig) G and IgM subclasses,
directed against a platelet-associated antigen, lead to destruction of
platelets in spleen, liver.
• Acute disorder more common in childhood, typically following viral illness;
has good prognosis with 80% to 90% recovering uneventfully. Typically
lasts 1 to 2 months.
• Chronic disorder (more than 6-month course) most common between
ages 20 and 40, three times more common in women, may last for years
or even indefinitely. May be associated with pregnancy or with
development of systemic lupus erythematosus or thyroid disease.

74. Clinical Manifestations
• Bruising, petechiae, bleeding from nares and gums,
menorrhagia.
Diagnostic Evaluation
• CBC demonstrates platelet count less than 20,000/mm3
(acute ITP); 30,000 to 70,000/mm3 (chronic ITP); may
also be lymphocytosis and eosinophilia.
• Bone marrow aspirate shows increased numbers of
young megakaryocytes, sometimes increased numbers
of eosinophils.
• Assay for platelet autoantibodies sometimes helpful.

75. Management
• Supportive care: judicious use of platelet
transfusions, control of bleeding.
• High-dose corticosteroids, I.V. immunoglobulins,
parenteral anti-D (for Rhesus positive patients
with spleens), azathioprine (Imuran),
cyclophosphamide (Cytoxan), vincristine
(Oncovin).
• Splenectomy removes potential site for
sequestration and destruction of platelets.

76. DISSEMINATED INTRAVASCULAR
COAGULATION
• DIC is an acquired thrombotic and hemorrhagic syndrome characterized
by abnormal activation of the clotting cascade and accelerated fibrinolysis.
This results in widespread clotting in small vessels with consumption of
clotting factors and platelets, so that bleeding and thrombosis occur
simultaneously.
Pathophysiology and Etiology
• A syndrome arising with an underlying disorder or event:
– Overwhelming infections, particularly bacterial sepsis.
– Obstetric complications: abruptio placentae, eclampsia, amniotic fluid
embolism, retention of dead fetus.
– Massive tissue injury: burns, trauma, fractures, major surgery, fat embolism,
organ destruction (eg, severe pancreatitis, hepatic failure).
– Vascular and circulatory collapse, shock.
• Hemolytic transfusion reaction.
• Snake bites.
• Malignancy: particularly lung, colon, stomach, pancreas.

77. Clinical Manifestations
• Signs of abnormal clotting:
– Coolness and mottling of extremities.
– Acrocyanosis (cold, mottled extremities with clear demarcation
from normal tissue).
– Dyspnea, adventitious breath sounds.
– Altered mental status.
– Acute renal failure.
– Pain (eg, related to bowel infarction).
• Signs of abnormal bleeding:
– Oozing, bleeding from sites of procedures, I.V. catheter insertion
sites, suture lines, mucous membranes, orifices.
– Internal bleeding leading to changes in vital organ function,
altered vital signs.

78. Diagnostic Evaluation
• Platelet count diminished.
• PT, PTT, and thrombin time prolonged.
• Fibrinogen decreased level.
• Fibrin split (degradation) products increased level.
• D-dimer fibrin degradation product increased level.
• Antithrombin III decreased level.
• Protein C decreased level.

79. Management
• Treat underlying disorder.
• Replacement therapy for serious hemorrhagic
manifestations:
– Fresh-frozen plasma replaces clotting factors.
– Platelet transfusions.
– Cryoprecipitate replaces clotting factors and fibrinogen.
• Supportive measures including fluid replacement,
oxygenation, maintenance of BP and renal perfusion.
• Heparin therapy (controversial) inhibits clotting
component of DIC.

80. VON WILLEBRAND'S DISEASE
• Inherited (autosomal dominant) or acquired bleeding
disorder characterized by decreased level of von
Willebrand factor and prolonged bleeding time.
Causes :
• von Willebrand factor synthesized in vascular
endothelium, megakaryocytes and platelets; enhances
platelet adhesion as first step in clot formation, also
acts as carrier of factor VIII in blood.
• von Willebrand's is most common inherited bleeding
disorder; includes multiple subtypes with varying
severity.

81. Clinical Manifestations
• Mucosal and cutaneous bleeding (eg, bruising, gingival bleeding,
epistaxis, menorrhagia).
• Prolonged bleeding from cuts or after dental and surgical
procedures.
Diagnostic Evaluation
• Bleeding time—prolonged.
• Ristocetin cofactor—abnormal.
• von Willebrand's factor—decreased.
• von Willebrand's factor multimers—demonstrate defective von
Willebrand's factor in some types.
• Factor VIII—generally decreased.

82. Management
• Replacement of von Willebrand's factor and factor VIII
using clotting factor concentrates (Alphanate, Humate-P).
• Antifibrinolytic medications (Amicar, tranexamic acid) to
stabilize clot formation before dental procedures and
before minor surgery.
• Desmopressin acetate (DDAVP), a synthetic analogue of
vasopressin, may be used to manage mild to moderate
bleeding.
• Estrogen and progesterone stimulate production of von
Willebrand's factor and Factor VIII and may be particularly
helpful in control of menorrhagia.