Hematology - Clinical

What gender and type of insect is responsible for transmitting malaria?

Plasmodia transmitted by female Anopheles mosquitos

What is the process for infection of malaria within the body?

Sporozoites infect liver and RBCs → trophozoite divides asexually in RBCs → RBCs lyse → chills, fever → merozoites infect other RBCs

There are 4 types of plasmodia that can infect someone with malaria. What are they called and what are the differences in symptoms?

P. vivax & P. ovale: chills and fever every 48 hours

P. malariae: chills and fever every 72 hours

P. falciparum: no pattern but the most severe → CNS involvement (seizures, coma, renal failure)

What are the clinical features of malaria and how is it investigated and treated?

Sx: high fever, shaking chills, hepatosplenomegaly, thrombocytopenia without leukocytes, abdominal pain, diarrhea, myalgia, headaches

Microscopy of blood samples every 12-24h (thick and thin smears)

Tx: hydroxychloroquine

What is phlebitis? What are it’s clinical features?

= inflammation of veins, commonly in legs. Can be caused by IV catheter insertion, local trauma, irritating medications

Redness, swelling, pain along the vein. Hard, cord-like vein

How is phlebitis treated?

NSAIDs, local compression, antibiotics (if bacterial)

What type of bacteria is septicaemia often caused by?

What is the process of how septicaemia invades the body and causes such mass destruction?

Commonly due to gram - bacteria (E. coli)

Bacterial endotoxins damage endothelial cells→ vasodilation. Activation of complement pathway → histamine release → vascular leakage. Cytokines (IL-1, TNF) cause massive vasodilation → shock, DIC

Warm skin, bounding pulse, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) → bleeding and thrombosis. Fever, chills, tachycardia, tachypnea, confusion.

What condition causes these signs and symptoms?

Septicemia

What investigations and treatment are standard in septicaemia?

CBC, electrolytes, BUN, creatinine, liver enzymes, blood cultures

IV fluids, oxygen, IV antibiotics, send to ER

What is lymphadenitis, what is it caused by and what are its clinical features?

Inflammation/enlargement fo lymph nodes

Caused by infections, malignancies, draining abscess

Painful/tender nodes → most likely infectious

Fluctuant, warm nodes → likely an abscess

Gram stain, CBC (increased WBCs), mono spot, PPD (TB), ultrasound. Treatment depends on the cause → antimicrobials, chemotherapy, or radiation

These investigations and treatments would be ordered for someone with what condition?

Lymphadenitis

What is lymphedema and describe both primary and secondary.

Fluid accumulation due to lymphatic obstruction

Primary: congenital

Secondary: infection, malignancy, obesity, radiation, surgery

What are the clinical features of lymphedema and how is it typically treated?

Non-pitting edema, impaired mobility, discomfort

First-line treatment: physical therapy, compression therapy. Hygiene and skin care to prevent infections

Inflammation of lymphatic channels due to infection distal to the channel.

What condition does the above describe and what is it most commonly caused by?

Lymphangitis, most commonly caused by strep pyogenes

True or false: lymphangitis often spreads from cellulitis

True

How would lymphangitis be investigated and what is the treatment?

CBC (marked leukocytosis), blood cultures

Parenteral antibiotics, analgesics, incision and drainage if abscess present

Supportive treatment: hot compress, elevation, immobilization

What is aplastic anemia and what is it caused by?

Bone marrow failure → pancytopenia

Caused by: idiopathic, medications (chemo, chloramphenicol), infections (EBV, HIV), SLE, radiation

Fever (infection), pallor, petechaie, fatigue, ± splenomegaly. In what conditions would these signs and symptoms be present?

Aplastic anemia

How is aplastic anemia treated and investigated?

Remove offending agents, antibiotics, bone marrow transplant

CBC: pancytopenia, decreased reticulocytes

Bone marrow biopsy: hypocellularity, fat replacement

Premature RBC destruction leads to compensatory bone marrow hyperplasia. What disease is this?

Hemolytic anemia

What are the various types of intrinsic (hereditary) hemolytic anemia?

Membrane defects: hereditary spherocytosis

Enzyme deficiencies: G6PD deficiency, pyruvate kinase deficiency

Hemoglobinopathies: sickle cell disease, thalassemia

What are the various types of extrinsic (acquired causes) hemolytic anemia?

Autoimmune: warm (ing) and cold (IgM) hemolysis

Drug-induced, mechanical (prosthetic valves), infections (malaria, clostridium)

Alloimmune: hemolytic transfusion reaction, Rh hemolytic disease of the newborn

What are the differences between warm and hold hemolysis, as it relates to being a cause of hemolytic anemia?

Hot: IgG

Cold: IgM

What are some of the common clinical features of hemolytic anemia?

Jaundice (unconjugated hyperbilirubinemia), hepatosplenomegaly, dark urine, iron overload (extravascular hemolysis) or iron deficiency (intravascular hemolysis)

Are schistocytes seen on labs in intravascular hemolysis or extravascular?

Intravascular

What kinds of tests would be done on a patient with suspected hemolytic anemia? What would the anticipated results be?

CBC (increased reticulocytes), blood film, decreased haptoglobin, increased LDH, increased unconjugated bilirubin, Coombs test

What is the difference between a direct and indirect Coombs test?

Direct: detects IgG/complement on RBCs (autoimmune)

Indirect: detects antibodies in serum

Stop offending drugs, corticosteroids, IV immunoglobulin, splenectomy. Iron and folic acid supplementation, transfusions in serious cases.

What disease would these treatments be indicated for?

Hemolytic anemia

This disease is characterized by enlarged RBCs (MCV > 100fl).

Macrocytic anemia

What are the two main types of macrocytic anemia?

Megaloblastic → due to defective DNA synthesis

Non-megaloblastic → due to abnormal RBC membrane expansion

What are a few common causes of megaloblastic macrocytic anemia?

B12 deficiency, folate deficiency, congenital enzyme defects

Fatigue, pallor, glossitis, diarrhea, weight loss. Neurological symptoms (B12 deficiency only) that include peripheral neuropathy, subacute combine degeneration of the spinal cord. Mild jaundice

What disease would these symptoms be indicative of?

Megaloblastic macrocytic anemia

What lab results would you expect to see for a patient with megaloblastic macrocytic anemia?

high MCV on CBC, deceased reticulocytes, hyperhsegmented neutrophils on blood smear.

How can one differentiate between b12 and folate deficiency by MMA and homocysteine lab values?

if increased MMA and homocysteine → B12 deficiency

if normal MMA and increased homocysteine → folate deficiency

What are the treatments for vitamin B12 deficiency and folate deficiency?

IM b12 injections for life

oral folic acid 1-5mg daily

Pernicious anemia is a subtype of what kind of anemia?

Megaloblastic

Autoimmune disorder causing vitamin b12 deficiency. Autoantibodies against gastric parietal cells causing achlorhydria meaning that no IF is produced. B12 can’t be absorbed.

This is more common in older adults, women and Northern Europeans.

What disease is this?

Pernicious anemia

What are some of the neurological symptoms that are unique to B12 deficiency?

Peripheral neuropathy, subacute combine degeneration of the spinal cord: dorsal column involvement (loss of proprioception, vibration sense, ataxia) and lateral column involvement (muscle weakness, spasticity)

What would the results be on the following tests in the case of pernicious anemia?

MCV, reticulocytes, blood smear, serum b12, MMA and homocysteine

Intrinsic factor antibody test, parietal cell antibodies

MCV high, reticulocytes low, blood smear shows oval microcytes and hypersegmented neutrophils, b12 low

MMA and homocysteine high, intrinsic factor antibody test positive, parietal cell antibodies usually positive

First-line: Lifelong IM vitamin B12 injections (1000mcg IM daily for 1 week, then weekly for 1 month, then monthly for life). Oral high dose B12 (if no severe neurological symptoms and absorption intact). Monitor neurological symptoms closely → damage may be irreversible if untreated for too long.

What condition would these treatments be applicable for?

Pernicious anemia

• Alcoholism (direct toxic effect on erythropoiesis), liver disease, hypothyroidism (decreased erythropoiesis), drugs (hydroxyurea, zidovudine, chemotherapy)

Clinical features: no hyperhsegmented neutrophils. Mild anemia, possible hepatosplenomegaly (liver disease-related)

These are causes and clinical features of what condition?

Non-megaloblastic macrocytic anemia

What would you expect to see on investigations and how would you treat for non0megaloblastic macrocytic anemia?

CBC: increased MCV, normal reticulocytes

Peripheral blood smear: large, round RBCs, but normal neutrophils

Tx: treat underlying cause (alcohol cessation, thyroid HRT, supportive care)

What is post-hemorrhagic anemia?

Blood loss (acute or chronic) that leads to anemia

Is chronic or acute blood loss better tolerated?

Chronic is better tolerated, as it leads to increased erythropoiesis. Acute can cause hypovolemia → shock → death

What would you expect to see on labs for a patient with post-hemorrhage anemia?

Decreased Hct, decreased Hb, reticulocytosis (if bone marrow response is intact)

True of false: iron deficiency anemia is the most common anemia in the world?

True

What is iron deficiency anemia caused by?

Blood loss: GI bleeding, menorrhagia

Increased utilization: pregnancy, lactation, infants/children

Malabsorption: celiac disease, IBD

Dietary deficiency: vegan diet, chronic malnutrition

Fatigue, pallor, weakness, irritability, palpitations, headaches, brittle nails, koilonychia (spoon nails), pica, plummer-vinson syndrome (dysphagia, esophageal webs, glossitis).

What condition would cause these symptoms?

Iron deficiency anemia

What would you expect to see on labs in IDA?

Decreased MCV, MCH

Increased RDW

Decreased ferritin, serum iron, iron saturation

Increased TIBC

What is anemia of chronic disease and what is the pathophysiology?

Commonly seen in hospitalized patients and those with chronic illness

Leads to inflammatory cytokine release (IL-1, IL-6, TNF-a, IFN-y) leading to: decreased iron availability, decreased EPO production, decreased RBC lifespan (70-80 vs the normal 120)

What are some common causes of ACD?

Endocrine: CKD, hypothyroidism, hypogonadism

Malignancies: Hodgkin’s lymphoma, breast cancer, lung cancer, multiple myeloma

Chronic inflammatory diseases: RA, SLE, IBD, vasculitis

Tb, HIV, abscesses

Symptoms of underlying disease, mild-moderate anemia symptoms, no specific physical signs

What are these clinical signs of ?

ACD

How is ACD treated?

Treat the underlying chronic disease. If anemia caused by CKD, give erythropoiesis-stimulating agents

What would you expect to see on labs for ACD?

mild normocytic or microcytic anemia

Low iron, TIBC

normal or high ferritin

serum EPO level: low (except in CKD where EPO production is severely reduced)

high ESR, CRP, fibrinogen

Thalassemia is an inherited hemoglobin disorder characterized by what?

decreased or absent global chain synthesis

There are 4 different type of gene deletions in a-thalassemia. Describe them

1 gene deletion: clinically silent

2 gene deletions: mild anemia

3 gene deletions: HbH disease, severe anemia, splenomegaly

4 gene deletions: hydros fettles (fatal in utero)

Minor b-thalassemia and major b-thalassemia exist. What are the differences?

minor: mild anemia, usually asymptomatic

major (Cooley’s anemia): severe anemia, hepatosplenomegaly, iron overload

What are the clinical features of thalassemia and what would you expect to see on labwork?

Jaundice, hepatosplenomegaly, iron overload, bone deformities. Severe cases require lifelong transfusions

Decreased MCV, decreased Hb, increased RBC count

Hb electrophoresis: increased HbF and decreased HbA

Transfusions for severe cases, iron chelation therapy, bone marrow transplant for major.

In what disease would you expect to see these lab values?

Thalassemias

What populations are thalassemia an and b common in?

a = southeast asians, africans

b = mediterranean populations

X-linked recessive disorder. Deficient enzyme = RBCs are susceptible to oxidative stress. Common in mediterranean, African and asian populations

G6P6 deficiency

What are some common triggers of G6PD deficiency and what are the clinical features?

Triggers: infections, drugs (dapsone, nitrofurantoin, antimalarials, sulfonamides), fava beans

Clinical features: sudden onset hemolysis → back pain, hemoglobinuria (dark urine) within 2-3 days of trigger. Jaundice, pallor, splenomegaly in severe cases

Blood smear: Heinz bodies, bite cells

G6PD enzyme assay (done after hemolysis resolves)

Tx: avoid oxidative triggers, blood transfusion if severe

In what disease would you expect to see these lab values?

G6PD deficiency

Excessive iron storage and absorption → iron overload → organ damage. Autosomal recessive mutation in HFE gene. Leads to unregulated intestinal iron absorption, increasing total body iron stores to 20-40g (normal = about 1g)

Most common in North European ancestry and symptoms typically appear it the 40s-50s (earlier in men due to lack of menstrual iron loss)

What condition is the above describing?

Hemochromatosis

What are the differences between primary and secondary hemochromatosis?

Primary (hereditary): HFE gene mutation

Secondary (acquired): due to multiple blood transfusions, chronic liver disease, hemolytic anemia

What is the classic triad of hemochromatosis?

• Bronze skin pigmentation (bronze diabetes)

• Diabetes mellitus (b-cell destruction)

• Cirrhosis (iron deposition in hepatocytes, increases risk of hepatocellular carcinoma by 200x)

What would be the appropriate investigations for hemochromatosis and their respective values?

Increased serum iron, decreased TIBC, increased T sat, increased ferritin

Genetic testing (HFE mutation analysis) to confirm primary hemochromatosis

Liver biopsy to confirm iron deposition in hepatocytes

MRI of liver (T2-weighted imaging) to detect iron overload non-invasively

What are the treatments for hemochromatosis?

Therapeutic phlebotomy (first-line, most effective): weekly blood removal until ferritin normalizes

Iron chelation therapy (for patients who cannot undergo phlebotomy)

Avoid iron-rich foods, alcohol, vitamin C supplements

Monitor for cirrhosis and hepatocellular carcinoma

True or false: sickle cell disease is an autosomal dominant disorder

False, it is an autosomal recessive disorder

Sick-shaped RBCs lead to what?

Vaso-occlusion and hemolysis

What disease are these clinical features symbolic of?

Pain, hand-foot syndrome in infants, stroke, acute chest syndrome. Chronic hemolysis: jaundice, gallstones, anemia. Rapidly enlarging spleen, sudden anemia

Sickle cell disease

What would confirm the diagnosis of sickle cell disease? How is sickle cell treated?

Hb electrophoresis

Hydration, oxygen, pain control, transfusions if severe, hydroxyurea for crisis prevention

What is idiopathic thrombocytopenia purpura and in what population is it common in?

autoimmune platelet destruction in spleen. common in children post-viral infection

What are the clinical features of idiopathic thrombocytopenia purpura, what would you find on investigations and how is it treated?

Petechaie, bruising, epistaxis, NO hepatosplenomegaly

Decreased platelets, normal PT/PTT

Treatment is self-limiting, IVIG or corticosteroids if severe

What is disseminated intravascular coagulation and what causes it?

Systemic activation of coagulation → widespread clotting and bleeding

Caused by infection, malignancy, trauma, transfusion reactions

Bleeding (petechiae, epistaxis, intracranial hemorrhage), hypovolemic shock.

What condition do these symptoms point towards?

Disseminated intravascular coagulation

What would you expect to find on labs in the case of DIC and how would you treat?

Increased PT/PTT, decreased fibrinogen, increased d-dimer

Treat the underlying cause, transfusions

Is hemophilia X or Y-linked recessive?

X-linked

What factor deficiency is unique to hemophilia A and B?

Hemophilia A: Factor 8 deficiency

Hemophilia B: Factor 9 deficiency

Spontaneous hemorrhage, hemarthrosis (joint bleeds → arthritis), easy bruising, prolonged bleeding after minor trauma.

Increased PTT, normal PT/INR

What disease is this characteristic of?

Hemophilia

What is the treatment for hemophilia?

Desmopressin (mild hemophilia A), Factor 8 or 9 replacement

What is the most common vasculitis in children (peak age 4-10 years) and what is the pathophysiology?

Henonch-Schoenlein purpura

IgA-mediated immune complex deposition in small vessels → inflammation in skin, GI tract, kidneys and joints

HSP often follows what kind of infection? What are some other triggers?

URTI

Vaccinations, medications, cold exposures

What is the HSP tetrad?

Palpable purpura, arthritis/arthralgia, abdominal pain, renal involvement

What investigations should be done for suspected HSP?

CBC, coagulation panel, U/A (hematuria, proteinuria, RBC casts), serum IgA increased, renal biopsy and abdominal ultrasound

How is HSP diagnosed?

It is a clinical diagnosis

How is HSP treated?

supportive care (mainstay), corticosteroid in severe cases, monitor urine and BP for 6 months to check for nephritis progression

What is the prognosis for HSP?

Usually self-limiting in about 4 weeks

True or false: von Willebrand disease is autosomal dominant?

True

Defection vWF in von Willebrand disease results in what?

Impaired platelet adhesion

What are the clinical features of vWD?

Mucosal bleeding (epistaxis, menorrhagia, gingival bleeding). Easy bruising, prolonged bleeding time

increased PTT, normal PT, decreased vWF antigen. In what condition would you expect to see the lab results?

von Willebrand disease

Compare and contrast polycythemia vera and secondary polycythemia

What deficiency characterizes erythropoietic protoporphyria?

Deficiency of ferrochelatase enzyme → accumulation of protoporphyrin in erythrocytes, plasma, liver and skin

What causes severe phytotoxic skin reactions upon light exposure?

Protoporphyrin

What are the clinical features of EPP?

• Painful, burning and stinging sensation within minutes of sun exposure

• Redness, swelling and erythema without blistering

• Thickened skin, scarring and leathery appearance over time with chronic exposure

What would you expect to see on labs in EPP?

• Total erythrocyte protoporyphin would be markedly increased

• Plasma fluorescence peak at 635 nm (diagnostic)

• LFTs (disease can result in liver damage)

• Abdominal ultrasound if gallstones suspected

What treatments should be recommended for someone with EPP?

• Sun protection (most important), and possibly beta-carotene (may reduce photosensitivity)

• Cholestyramine or activated charcoal (increases protophyrin excretion in bile)

• Liver transplant in severe cases with liver failure

What deficiency is acute intermittent porphyria characterized by?

Porphobilinogen deaminage

Accumulation of neurotoxic porphyrin precursors → acute neurovisceral attacks

What are some common triggers for acute intermittent porphyria?

• Drugs (barbiturates, sulphonamides, rifampin, anti epileptics)

• Fasting or carbohydrate restriction

• Infections, stress, alcohol, smoking, menstruation